@article{gettings_self_mcmahan_brown_nordone_yabsley_2020, title={Local and regional temporal trends (2013-2019) of canine Ehrlichia spp. seroprevalence in the USA}, volume={13}, ISSN={["1756-3305"]}, DOI={10.1186/s13071-020-04022-4}, abstractNote={Abstract}, number={1}, journal={PARASITES & VECTORS}, author={Gettings, Jenna R. and Self, Stella C. W. and McMahan, Christopher S. and Brown, D. Andrew and Nordone, Shila K. and Yabsley, Michael J.}, year={2020}, month={Mar} }
 @article{gettings_self_mcmahan_brown_nordone_yabsley_2020, title={Regional and Local Temporal Trends of Borrelia burgdorferi and Anaplasma spp. Seroprevalence in Domestic Dogs: Contiguous United States 2013-2019}, volume={7}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2020.561592}, abstractNote={In 2019, in the United States, over 220,000 and 350,000 dogs tested positive for exposure to Anaplasma spp. and Borrelia burgdorferi, respectively. To evaluate regional and local temporal trends of pathogen exposure we used a Bayesian spatio-temporal binomial regression model, analyzing serologic test results for these pathogens from January 2013 to December 2019. Regional trends were not static over time, but rather increased within and beyond the borders of historically endemic regions. Increased seroprevalence was observed as far as North Carolina and North Dakota for both pathogens. Local trends were estimated to evaluate the heterogeneity of underlying changes. A large cluster of counties with increased B. burgdorferi seroprevalence centered around West Virginia, while a similar cluster of counties with increased Anaplasma spp. seroprevalence centered around Pennsylvania and extended well into Maine. In the Midwest, only a small number of counties experienced an increase in seroprevalence; instead, most counties had a decrease in seroprevalence for both pathogens. These trends will help guide veterinarians and pet owners in adopting the appropriate preventative care practices for their area. Additionally, B. burgdorferi and A. phagocytophilum cause disease in humans. Dogs are valuable sentinels for some vector-borne pathogens, and these trends may help public health providers better understand the risk of exposure for humans.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Gettings, Jenna R. and Self, Stella C. W. and McMahan, Christopher S. and Brown, D. Andrew and Nordone, Shila K. and Yabsley, Michael J.}, year={2020}, month={Oct} }
 @misc{self_liu_nordone_yabsley_walden_lund_bowman_carpenter_mcmahan_gettings_2019, title={Canine vector-borne disease: mapping and the accuracy of forecasting using big data from the veterinary community}, volume={20}, ISSN={["1475-2654"]}, DOI={10.1017/S1466252319000045}, abstractNote={Abstract}, number={1}, journal={ANIMAL HEALTH RESEARCH REVIEWS}, author={Self, Stella C. W. and Liu, Yan and Nordone, Shila K. and Yabsley, Michael J. and Walden, Heather S. and Lund, Robert B. and Bowman, Dwight D. and Carpenter, Christopher and McMahan, Christopher S. and Gettings, Jenna R.}, year={2019}, month={Jun}, pages={47–60} }
 @article{liu_nordone_yabsley_lund_mcmahan_gettings_2019, title={Quantifying the relationship between human Lyme disease and Borrelia burgdorferi exposure in domestic dogs}, volume={14}, ISSN={["1970-7096"]}, DOI={10.4081/gh.2019.750}, abstractNote={Lyme disease (LD) is the most common vector-borne disease in the United States. Early confirmatory diagnosis remains a challenge, while the disease can be debilitating if left untreated. Further, the decision to test is complicated by under-reporting, low positive predictive values of testing in non-endemic areas and travel, which together exacerbate the difficulty in identification of newly endemic areas or areas of emerging concern. Spatio-temporal analyses at the national scale are critical to establishing a baseline human LD risk assessment tool that would allow for the detection of changes in these areas. A well-established surrogate for human LD incidence is canine LD seroprevalence, making it a strong candidate covariate for use in such analyses. In this paper, Bayesian statistical methods were used to fit a spatio-temporal spline regression model to estimate the relationship between human LD incidence and canine seroprevalence, treating the latter as an explanatory covariate. A strong non-linear monotonically increasing association was found. That is, this analysis suggests that mean incidence in humans increases with canine seroprevalence until the seroprevalence in dogs reaches approximately 30%. This finding reinforces the use of canines as sentinels for human LD risk, especially with respect to identifying geographic areas of concern for potential human exposure.}, number={1}, journal={GEOSPATIAL HEALTH}, author={Liu, Yan and Nordone, Shila K. and Yabsley, Michael J. and Lund, Robert B. and McMahan, Christopher S. and Gettings, Jenna R.}, year={2019}, pages={111–120} }
 @article{liu_watson_gettings_lund_nordone_yabsley_mcmahan_2017, title={A Bayesian spatio-temporal model for forecasting Anaplasma species seroprevalence in domestic dogs within the contiguous United States}, volume={12}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0182028}, abstractNote={This paper forecasts the 2016 canine Anaplasma spp. seroprevalence in the United States from eight climate, geographic and societal factors. The forecast’s construction and an assessment of its performance are described. The forecast is based on a spatial-temporal conditional autoregressive model fitted to over 11 million Anaplasma spp. seroprevalence test results for dogs conducted in the 48 contiguous United States during 2011–2015. The forecast uses county-level data on eight predictive factors, including annual temperature, precipitation, relative humidity, county elevation, forestation coverage, surface water coverage, population density and median household income. Non-static factors are extrapolated into the forthcoming year with various statistical methods. The fitted model and factor extrapolations are used to estimate next year’s regional prevalence. The correlation between the observed and model-estimated county-by-county Anaplasma spp. seroprevalence for the five-year period 2011–2015 is 0.902, demonstrating reasonable model accuracy. The weighted correlation (accounting for different sample sizes) between 2015 observed and forecasted county-by-county Anaplasma spp. seroprevalence is 0.987, exhibiting that the proposed approach can be used to accurately forecast Anaplasma spp. seroprevalence. The forecast presented herein can a priori alert veterinarians to areas expected to see Anaplasma spp. seroprevalence beyond the accepted endemic range. The proposed methods may prove useful for forecasting other diseases.}, number={7}, journal={PLOS ONE}, author={Liu, Yan and Watson, Stella C. and Gettings, Jenna R. and Lund, Robert B. and Nordone, Shila K. and Yabsley, Michael J. and McMahan, Christopher S.}, year={2017}, month={Jul} }
 @article{watson_liu_lund_gettings_nordone_mcmahan_yabsley_2017, title={A Bayesian spatio-temporal model for forecasting the prevalence of antibodies to Borrelia burgdorferi, causative agent of Lyme disease, in domestic dogs within the contiguous United States}, volume={12}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0174428}, abstractNote={This paper models the prevalence of antibodies to Borrelia burgdorferi in domestic dogs in the United States using climate, geographic, and societal factors. We then use this model to forecast the prevalence of antibodies to B. burgdorferi in dogs for 2016. The data available for this study consists of 11,937,925 B. burgdorferi serologic test results collected at the county level within the 48 contiguous United States from 2011-2015. Using the serologic data, a baseline B. burgdorferi antibody prevalence map was constructed through the use of spatial smoothing techniques after temporal aggregation; i.e., head-banging and Kriging. In addition, several covariates purported to be associated with B. burgdorferi prevalence were collected on the same spatio-temporal granularity, and include forestation, elevation, water coverage, temperature, relative humidity, precipitation, population density, and median household income. A Bayesian spatio-temporal conditional autoregressive (CAR) model was used to analyze these data, for the purposes of identifying significant risk factors and for constructing disease forecasts. The fidelity of the forecasting technique was assessed using historical data, and a Lyme disease forecast for dogs in 2016 was constructed. The correlation between the county level model and baseline B. burgdorferi antibody prevalence estimates from 2011 to 2015 is 0.894, illustrating that the Bayesian spatio-temporal CAR model provides a good fit to these data. The fidelity of the forecasting technique was assessed in the usual fashion; i.e., the 2011-2014 data was used to forecast the 2015 county level prevalence, with comparisons between observed and predicted being made. The weighted (to acknowledge sample size) correlation between 2015 county level observed prevalence and 2015 forecasted prevalence is 0.978. A forecast for the prevalence of B. burgdorferi antibodies in domestic dogs in 2016 is also provided. The forecast presented from this model can be used to alert veterinarians in areas likely to see above average B. burgdorferi antibody prevalence in dogs in the upcoming year. In addition, because dogs and humans can be exposed to ticks in similar habitats, these data may ultimately prove useful in predicting areas where human Lyme disease risk may emerge.}, number={5}, journal={PLOS ONE}, author={Watson, Stella C. and Liu, Yan and Lund, Robert B. and Gettings, Jenna R. and Nordone, Shila K. and McMahan, Christopher S. and Yabsley, Michael J.}, year={2017}, month={May} }
 @article{tokarz_heffelfinger_jima_gerlach_shah_rodriguez-nunez_kortum_fletcher_nordone_law_et al._2017, title={Disruption of Trim9 function abrogates macrophage motility in vivo}, volume={102}, ISSN={0741-5400 1938-3673}, url={http://dx.doi.org/10.1189/jlb.1A0816-371R}, DOI={10.1189/jlb.1a0816-371r}, abstractNote={Abstract}, number={6}, journal={Journal of Leukocyte Biology}, publisher={Wiley}, author={Tokarz, Debra A. and Heffelfinger, Amy K. and Jima, Dereje D. and Gerlach, Jamie and Shah, Radhika N. and Rodriguez-Nunez, Ivan and Kortum, Amanda N. and Fletcher, Ashley A. and Nordone, Shila K. and Law, J. McHugh and et al.}, year={2017}, month={Oct}, pages={1371–1380} }
 @article{levine_cianciolo_linder_bizikova_birkenheuer_brooks_salous_nordone_bellinger_marr_et al._2017, title={Endothelial alterations in a canine model of immune thrombocytopenia}, volume={30}, ISSN={0953-7104 1369-1635}, url={http://dx.doi.org/10.1080/09537104.2017.1378807}, DOI={10.1080/09537104.2017.1378807}, abstractNote={Abstract Bleeding heterogeneity amongst patients with immune thrombocytopenia (ITP) is poorly understood. Platelets play a role in maintaining endothelial integrity, and variable thrombocytopenia-induced endothelial changes may influence bleeding severity. Platelet-derived endothelial stabilizers and markers of endothelial integrity in ITP are largely underexplored. We hypothesized that, in a canine ITP model, thrombocytopenia would lead to alterations in the endothelial ultrastructure and that the Von Willebrand factor (vWF) would serve as a marker of endothelial injury associated with thrombocytopenia. Thrombocytopenia was induced in healthy dogs with an antiplatelet antibody infusion; control dogs received an isotype control antibody. Cutaneous biopsies were obtained prior to thrombocytopenia induction, at platelet nadir, 24 hours after nadir, and on platelet recovery. Cutaneous capillaries were assessed by electron microscopy for vessel thickness, the number of pinocytotic vesicles, the number of large vacuoles, and the number of gaps between cells. Pinocytotic vesicles are thought to represent an endothelial membrane reserve that can be used for repair of damaged endothelial cells. Plasma samples were assessed for vWF. ITP dogs had significantly decreased pinocytotic vesicle numbers compared to control dogs (P = 0.0357) and the increase in plasma vWF from baseline to 24 hours correlated directly with the endothelial large vacuole score (R = 0.99103; P < 0.0001). This direct correlation between plasma vWF and the number of large vacuoles, representing the vesiculo-vacuolar organelle (VVO), a permeability structure, suggests that circulating vWF could serve as a biomarker for endothelial alterations and potentially a predictor of thrombocytopenic bleeding. Overall, our results indicate that endothelial damage occurs in the canine ITP model and variability in the degree of endothelial damage may account for differences in the bleeding phenotype among patients with ITP.}, number={1}, journal={Platelets}, publisher={Informa UK Limited}, author={LeVine, Dana N. and Cianciolo, Rachel E. and Linder, Keith E. and Bizikova, Petra and Birkenheuer, Adam J. and Brooks, Marjory B. and Salous, Abdelghaffar K. and Nordone, Shila K. and Bellinger, Dwight A. and Marr, Henry and et al.}, year={2017}, month={Nov}, pages={88–97} }
 @article{bowman_liu_mcmahan_nordone_yabsley_lund_2016, title={Forecasting United States heartworm Dirofilaria immitis prevalence in dogs}, volume={9}, ISSN={["1756-3305"]}, DOI={10.1186/s13071-016-1804-y}, abstractNote={This paper forecasts next year's canine heartworm prevalence in the United States from 16 climate, geographic and societal factors. The forecast's construction and an assessment of its performance are described.The forecast is based on a spatial-temporal conditional autoregressive model fitted to over 31 million antigen heartworm tests conducted in the 48 contiguous United States during 2011-2015. The forecast uses county-level data on 16 predictive factors, including temperature, precipitation, median household income, local forest and surface water coverage, and presence/absence of eight mosquito species. Non-static factors are extrapolated into the forthcoming year with various statistical methods. The fitted model and factor extrapolations are used to estimate next year's regional prevalence.The correlation between the observed and model-estimated county-by-county heartworm prevalence for the 5-year period 2011-2015 is 0.727, demonstrating reasonable model accuracy. The correlation between 2015 observed and forecasted county-by-county heartworm prevalence is 0.940, demonstrating significant skill and showing that heartworm prevalence can be forecasted reasonably accurately.The forecast presented herein can a priori alert veterinarians to areas expected to see higher than normal heartworm activity. The proposed methods may prove useful for forecasting other diseases.}, journal={PARASITES & VECTORS}, author={Bowman, Dwight D. and Liu, Yan and McMahan, Christopher S. and Nordone, Shila K. and Yabsley, Michael J. and Lund, Robert B.}, year={2016}, month={Oct} }
 @article{levine_birkenheuer_brooks_nordone_bellinger_jones_fischer_oglesbee_frey_brinson_et al._2014, title={A novel canine model of immune thrombocytopenia: has immune thrombocytopenia (ITP) gone to the dogs?}, volume={167}, ISSN={0007-1048}, url={http://dx.doi.org/10.1111/bjh.13005}, DOI={10.1111/bjh.13005}, abstractNote={Summary}, number={1}, journal={British Journal of Haematology}, publisher={Wiley}, author={LeVine, Dana N. and Birkenheuer, Adam J. and Brooks, Marjory B. and Nordone, Shila K. and Bellinger, Dwight A. and Jones, Sam L. and Fischer, Thomas H. and Oglesbee, Stephen E. and Frey, Kahlina and Brinson, Nicole S. and et al.}, year={2014}, month={Jul}, pages={110–120} }
 @article{floras_holowaychuk_bienzle_bersenas_sharif_harvey_nordone_wood_2014, title={N-Terminal Pro-C-Natriuretic Peptide and Cytokine Kinetics in Dogs with Endotoxemia}, volume={28}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.12409}, abstractNote={BackgroundSerum N‐terminal pro‐C‐natriuretic peptide (NT‐proCNP) concentration at hospital admission has sufficient sensitivity and specificity to differentiate naturally occurring sepsis from nonseptic systemic inflammatory response syndrome (SIRS). However, little is known about serum NT‐proCNP concentrations in dogs during the course of sepsis.}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Floras, A. N. K. and Holowaychuk, M. K. and Bienzle, D. and Bersenas, A. M. E. and Sharif, S. and Harvey, T. and Nordone, S. K. and Wood, G. A.}, year={2014}, pages={1447–1453} }
 @article{li_d’annibale-tolhurst_adler_fang_yin_birkenheuer_levy_jones_sung_hawkins_et al._2013, title={A Myristoylated Alanine-Rich C Kinase Substrate–Related Peptide Suppresses Cytokine mRNA and Protein Expression in LPS-Activated Canine Neutrophils}, volume={48}, ISSN={1044-1549 1535-4989}, url={http://dx.doi.org/10.1165/rcmb.2012-0278OC}, DOI={10.1165/rcmb.2012-0278oc}, abstractNote={Myristoylated alanine-rich C kinase substrate (MARCKS) is a ubiquitously expressed protein kinase C substrate that has emerged as a potential therapeutic target for the amelioration of mucin secretion and inflammation in patients with chronic obstructive pulmonary disease. MARCKS also plays a key role in regulating the adhesion, migration, and degranulation of neutrophils. Moreover, given its biological role in epithelial and immune cells, we hypothesized that MARCKS may play an integral role in cytokine secretion by neutrophils. Because the amino terminus of MARCKS is highly conserved across vertebrate species, we successfully applied the well-characterized human MARCKS inhibitory peptide, myristoylated N-terminal sequence (MANS), to attenuate the function of MARCKS in isolated canine neutrophils. Pretreatment of canine neutrophils with MANS peptide significantly reduced both mRNA and protein expression in a broad range of LPS-induced cytokines, including IL-8, a chemokine (C-X-C motif) ligand-1 orthologue, and TNF-α, in comparison with untreated cells or those treated with a control peptide. This reduction in cytokine expression was observed even when neutrophils were treated with MANS 2 hours after LPS exposure. The observed reduction in cytokine secretion was not attributable to protein retention or cell death, but was associated with reduced cytokine transcript synthesis. These observations identify MARCKS protein as a promising therapeutic target in the treatment of inflammatory diseases or syndromes attributed to neutrophil influx and inflammatory cytokine production, such as sepsis, acute lung injury, and acute respiratory distress syndrome.}, number={3}, journal={American Journal of Respiratory Cell and Molecular Biology}, publisher={American Thoracic Society}, author={Li, Jingjing and D’Annibale-Tolhurst, Melissa A. and Adler, Kenneth B. and Fang, Shijing and Yin, Qui and Birkenheuer, Adam J. and Levy, Michael G. and Jones, Samuel L. and Sung, Eui Jae and Hawkins, Eleanor C. and et al.}, year={2013}, month={Mar}, pages={314–321} }
 @article{stoeker_overman_nordone_moeser_simoes_dean_2013, title={Infection with feline immunodeficiency Virus alters intestinal epithelial transport and mucosal immune responses to probiotics}, volume={153}, ISSN={["0165-2427"]}, DOI={10.1016/j.vetimm.2013.01.017}, abstractNote={HIV infection is associated with intestinal mucosal dysfunction and probiotics offer the therapeutic potential to enhance the mucosal barrier in HIV+ patients. To evaluate the response of immunocompromised hosts to probiotics, we orally administered Lactobacillus acidophilus to cats with chronic feline immunodeficiency virus (FIV) infection. FIV infection significantly affected transcellular, but not paracellular, transport of small molecules across the intestinal epithelium. Additionally, probiotic treatment of FIV+ cats resulted in changes in cytokine release and mucosal leukocyte percentages that were not paralleled in FIV- cats. These results suggest a novel role for FIV in upregulating transcellular transport across the gastrointestinal epithelial barrier and demonstrate the potential therapeutic use of probiotic bacteria to restore intestinal homeostasis.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Stoeker, Laura L. and Overman, Elizabeth L. and Nordone, Shila K. and Moeser, Adam J. and Simoes, Rita D. and Dean, Gregg A.}, year={2013}, month={May}, pages={146–152} }
 @article{kajikawa_zhang_long_nordone_stoeker_lavoy_bumgardner_klaenhammer_dean_2012, title={Construction and Immunological Evaluation of Dual Cell Surface Display of HIV-1 Gag and Salmonella enterica Serovar Typhimurium FliC in Lactobacillus acidophilus for Vaccine Delivery}, volume={19}, ISSN={["1556-6811"]}, DOI={10.1128/cvi.00049-12}, abstractNote={ABSTRACT}, number={9}, journal={CLINICAL AND VACCINE IMMUNOLOGY}, author={Kajikawa, Akinobu and Zhang, Lin and Long, Julie and Nordone, Shila and Stoeker, Laura and LaVoy, Alora and Bumgardner, Sara and Klaenhammer, Todd and Dean, Gregg}, year={2012}, month={Sep}, pages={1374–1381} }
 @article{holowaychuk_birkenheuer_li_marr_boll_nordone_2012, title={Hypocalcemia and Hypovitaminosis D in Dogs with Induced Endotoxemia}, volume={26}, ISSN={["0891-6640"]}, DOI={10.1111/j.1939-1676.2012.00886.x}, abstractNote={BackgroundHypocalcemia is a documented electrolyte disturbance in people and animals with sepsis, but its mechanism is poorly understood.}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Holowaychuk, M. K. and Birkenheuer, A. J. and Li, J. and Marr, H. and Boll, A. and Nordone, S. K.}, year={2012}, pages={244–251} }
 @article{stoeker_nordone_gunderson_zhang_kajikawa_lavoy_miller_klaenhammer_dean_2011, title={Assessment of Lactobacillus gasseri as a Candidate Oral Vaccine Vector}, volume={18}, ISSN={["1556-6811"]}, DOI={10.1128/cvi.05277-11}, abstractNote={ABSTRACT}, number={11}, journal={CLINICAL AND VACCINE IMMUNOLOGY}, author={Stoeker, Laura and Nordone, Shila and Gunderson, Sara and Zhang, Lin and Kajikawa, Akinobu and LaVoy, Alora and Miller, Michael and Klaenhammer, Todd R. and Dean, Gregg A.}, year={2011}, month={Nov}, pages={1834–1844} }
 @article{wood_nordone_vaden_breitschwerdt_2011, title={Assessment of urine solute and matrix effects on the performance of an enzyme-linked immunosorbent assay for measurement of interleukin-6 in dog urine}, volume={23}, ISSN={["1040-6387"]}, DOI={10.1177/104063871102300219}, abstractNote={Measurement of cytokine concentrations within body fluids is a means of recognizing subclinical and/or unresolved, infectious and inflammatory states in patients. In the urinary tract, such information may be useful for identifying patients with pyelonephritis, asymptomatic bacteriuria, recurrent infections, and cystitis. One such cytokine, interleukin-6 (IL-6), is recognized as a primary cytokine that is produced following exposure of the urothelium to bacterial virulence factors. Complicating reliable testing for this and other cytokines is the nature of urine itself. Urine varies widely in its composition as indicated by the range of pH and urine specific gravity (USG) observed in healthy patients. An additional variable is the protein and carbohydrate matrix capable of hindering immunologic testing modalities, such as enzyme-linked immunosorbent assays (ELISAs). The purpose of the current study was to examine the role of urine pH, USG, and matrix while optimizing a canine-specific chemiluminescent ELISA for the measurement of IL-6 in the urine of dogs. Urine spiked with IL-6 obtained maximal IL-6 quantitative recoveries of only 55 ± 10% (mean ± 1 standard deviation) when an ELISA optimized for cell culture supernatants was used. The urine matrix and variations in USG were determined to by contributing to this poor IL-6 recovery. Using specific matrix inhibitors and optimal dilutions improved the IL-6 quantitative recovery to 91 ± 5%. Urine pH (5.5–9.5) had no effect. The current work underscores the importance of critically optimizing testing modalities for biomarkers, particularly if they are immunologic in origin.}, number={2}, journal={JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION}, author={Wood, Michael W. and Nordone, Sushila K. and Vaden, Shelly L. and Breitschwerdt, Edward B.}, year={2011}, month={Mar}, pages={316–320} }
 @article{kajikawa_nordone_zhang_stoeker_lavoy_klaenhammer_dean_2011, title={Dissimilar Properties of Two Recombinant Lactobacillus acidophilus Strains Displaying Salmonella FliC with Different Anchoring Motifs}, volume={77}, ISSN={["0099-2240"]}, DOI={10.1128/aem.05153-11}, abstractNote={ABSTRACT}, number={18}, journal={APPLIED AND ENVIRONMENTAL MICROBIOLOGY}, author={Kajikawa, Akinobu and Nordone, Shila K. and Zhang, Lin and Stoeker, Laura L. and LaVoy, Alora S. and Klaenhammer, Todd R. and Dean, Gregg A.}, year={2011}, month={Sep}, pages={6587–6596} }
 @article{li_birkenheuer_marr_levy_yoder_nordone_2011, title={Expression and function of triggering receptor expressed on myeloid cells-1 (TREM-1) on canine neutrophils}, volume={35}, ISSN={0145-305X}, url={http://dx.doi.org/10.1016/j.dci.2011.03.021}, DOI={10.1016/j.dci.2011.03.021}, abstractNote={The dog is both a valued veterinary species and a widely used translational model for sepsis research. However, relatively little work has been performed evaluating potential biomarkers present during canine infection. Triggering receptor expressed on myeloid cells-1 (TREM-1) has shown promise as a biomarker for infection and pneumonia in humans. Here we describe, for the first time, the expression and function of the canine orthologue of TREM-1. Expression of TREM-1 on canine neutrophils is significantly up-regulated by stimulation with microbial agonists of TLR2/6, TLR1/2, and TLR4/MD2. Kinetics of TREM-1 protein up-regulation are rapid, with significant increases observed within 2 hr of neutrophil activation. Functionally, canine TREM-1 synergistically enhances LPS-induced production of IL-8, TNF-α and a canine orthologue of CXCL1. Collectively, these data suggest that TREM-1 expression in dogs, as it is in humans, is an amplifier of pro-inflammatory responses to microbial products. These results have direct application to veterinary diagnostics as well as the potential to enhance the utility of canine disease models in the assessment of potential therapeutics in the treatment of human sepsis.}, number={8}, journal={Developmental & Comparative Immunology}, publisher={Elsevier BV}, author={Li, Jingjing and Birkenheuer, Adam J. and Marr, Henry S. and Levy, Michael G. and Yoder, Jeffrey A. and Nordone, Shila K.}, year={2011}, month={Aug}, pages={872–880} }
 @article{wendelsdorf_dean_hu_nordone_banks_2011, title={Host immune responses that promote initial HIV spread}, volume={289}, ISSN={["1095-8541"]}, DOI={10.1016/j.jtbi.2011.08.012}, abstractNote={The host inflammatory response to HIV invasion is a necessary component of the innate antiviral activity that vaccines and early interventions seek to exploit/enhance. However, the response is dependent on CD4+ T-helper cell 1 (Th1) recruitment and activation. It is this very recruitment of HIV-susceptible target cells that is associated with the initial viral proliferation. Hence, global enhancement of the inflammatory response by T-cells and dendritic cells will likely feed viral propagation. Mucosal entry sites contain inherent pathways, in the form of natural regulatory T-cells (nTreg), that globally dampen the inflammatory response. We created a model of this inflammatory response to virus as well as inherent nTreg-mediated regulation of Th1 recruitment and activation. With simulations using this model we sought to address the net effect of nTreg activation and its specific functions as well as identify mechanisms of the natural inflammatory response that are best targeted to inhibit viral spread without compromising initial antiviral activity. Simulation results provide multiple insights that are relevant to developing intervention strategies that seek to exploit natural immune processes: (i) induction of the regulatory response through nTreg activation expedites viral proliferation due to viral production by nTreg itself and not to reduced Natural Killer (NK) cell activity; (ii) at the same time, induction of the inflammation response through either DC activation or Th1 activation expedites viral proliferation; (iii) within the inflammatory pathway, the NK response is an effective controller of viral proliferation while DC-mediated stimulation of T-cells is a significant driver of viral proliferation; and (iv) nTreg-mediated DC deactivation plays a significant role in slowing viral proliferation by inhibiting T-cell stimulation, making this function an aide to the antiviral immune response.}, journal={JOURNAL OF THEORETICAL BIOLOGY}, author={Wendelsdorf, K. and Dean, G. and Hu, Shuhua and Nordone, S. and Banks, H. T.}, year={2011}, month={Nov}, pages={17–35} }
 @article{nordone_gookin_2010, title={Lymphocytes and not IFN-gamma mediate expression of iNOS by intestinal epithelium in murine cryptosporidiosis}, volume={106}, ISSN={["0932-0113"]}, DOI={10.1007/s00436-010-1837-7}, abstractNote={We hypothesized that unrecognized differences in epithelial expression of inducible nitric oxide synthase (iNOS), resulting from engineered immunodeficiency, could explain the contradictory findings of prior studies regarding the importance of nitric oxide (NO) in murine models of Cryptosporidium parvum infection. Severe combined immunodeficient mice (SCID) failed to constitutively or inducibly express epithelial iNOS or increase NO synthesis in response to C. parvum infection. In contrast, mice lacking IFN-γ alone induced both epithelial iNOS expression and NO synthesis in response to infection. Accordingly, lymphocytes mediate epithelial expression of iNOS and NO synthesis independent of IFN-γ in response to C. parvum infection. These findings in large part explain the contradictory conclusions of prior studies regarding the role of iNOS in C. parvum infection.}, number={6}, journal={PARASITOLOGY RESEARCH}, author={Nordone, Shila K. and Gookin, Jody L.}, year={2010}, month={May}, pages={1507–1511} }
 @article{lehman_kevin p. o'halloran_fallon_habermann_campbell_nordone_dean_hoover_avery_2009, title={Altered bone marrow dendritic cell cytokine production to toll-like receptor and CD40 ligation during chronic feline immunodeficiency virus infection}, volume={126}, ISSN={["1365-2567"]}, DOI={10.1111/j.1365-2567.2008.02907.x}, abstractNote={Summary}, number={3}, journal={IMMUNOLOGY}, author={Lehman, Tracy L. and Kevin P. O'Halloran and Fallon, Samantha A. and Habermann, Lindsey M. and Campbell, Jennifer A. and Nordone, Shila and Dean, Gregg A. and Hoover, Edward A. and Avery, Paul R.}, year={2009}, month={Mar}, pages={405–412} }
 @article{stoeker_nordone_lavoy_tallon_klaenhammer_dean_2009, title={Toll-like receptor activation profiles of wild-type, recombinant, and mutant Lactobacillus: implications for vaccine design}, volume={6}, ISSN={["1742-4690"]}, DOI={10.1186/1742-4690-6-s3-p133}, journal={RETROVIROLOGY}, author={Stoeker, L. and Nordone, S. and LaVoy, A. and Tallon, R. and Klaenhammer, T. and Dean, G.}, year={2009} }
 @article{nordone_ignacio_su_sempowski_golenbock_li_dean_2007, title={Failure of TLR4-driven NF-kappa B activation to stimulate virus replication in models of HIV type 1 activation}, volume={23}, ISSN={["0889-2229"]}, DOI={10.1089/aid.2007.0033}, abstractNote={The interaction of HIV-1 with Toll-like receptors (TLR) on host target cells is incompletely understood. Data from several in vivo and in vitro model systems suggest that TLR2, TLR4, and TLR9 remain functional and if stimulated, cause an upregulation of viral replication. In the present studies employing two different chronically HIV-1-infected cell lines and highly purified TLR agonists, we found ligation of TLR2 and TLR9, but not TLR4, resulted in significant upregulation of HIV-1 production. This result was not due to a lack of TLR4 expression or impaired NF-kappa B activation. Using HEK293 cells transfected with individual TLRs and an HIV-1 LTR reporter confirmed that TLR4 signaling does not directly activate the HIV-1 LTR. Finally, ultrapurified LPS did not enhance production of IL-1 beta or IL-6 in chronically infected U1 cells, whereas significant cytokine production was observed in uninfected U937 cells. These results confirm the biological activity of ultrapurified LPS and raise the possibility that TLR4 signaling pathways may be altered during chronic HIV-1 infection. Collectively, these studies suggest that although several TLR can upregulate NF-kappaB in HIV-1-infected cells, upregulation of NF-kappaB alone is insufficient to activate the viral LTR. Further dissection of the TLR signaling pathways is necessary to determine how TLR stimulation leads to LTR activation and whether HIV-1 infection can alter signaling through TLR4.}, number={11}, journal={AIDS RESEARCH AND HUMAN RETROVIRUSES}, author={Nordone, Sushila K. and Ignacio, Glicerio A. and Su, Lishan and Sempowski, Gregory D. and Golenbock, Douglas T. and Li, Liwu and Dean, Gregg A.}, year={2007}, month={Nov}, pages={1387–1395} }
 @article{ignacio_nordone_howard_dean_2005, title={Toll-like receptor expression in feline lymphoid tissues}, volume={106}, ISSN={["1873-2534"]}, DOI={10.1016/j.vetimm.2005.02.022}, abstractNote={Toll-like receptors (TLRs) are germline-encoded pattern recognition receptors (PRRs) that activate the innate immune system. While it is clear that TLRs are important in the immune response against pathogens, they may also be exploited by some pathogens. Our objective is to determine whether feline immunodeficiency virus (FIV) infection affects TLR expression or function thereby resulting in innate immune dysfunction. To this end, we cloned partial sequences for feline TLRs 1–3, 5–8, and developed real-time PCR assays to quantify feline TLRs 1–9. TLR expression was quantified in normal cat lymphoid tissues, purified lymphocyte subsets, and FIV-infected cell lines. Different expression patterns of TLRs were found in spleen, mesenteric lymph node, retropharyngeal lymph node, thymus, intestinal intraepithelial lymphocytes, and lamina propria lymphocytes. B lymphocytes, CD4+ T cells, and CD8+ T cells all expressed TLRs 2–5, 7–9; however, the relative levels of expression varied among lymphocyte phenotypes. Infection of cell lines with FIV resulted in altered TLR expression levels that differed depending on cell type. These results demonstrate that tissue distribution of TLRs is associated with the immunological role of a particular tissue, that lymphocytes may also express these ‘innate immune’ receptors, and that FIV infection can alter TLR expression.}, number={3-4}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Ignacio, G and Nordone, S and Howard, KE and Dean, GA}, year={2005}, month={Jul}, pages={229–237} }