@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} }