2021 journal article

Tumor Necrosis Factor Alpha-Induced Interleukin-1 Alpha Synthesis and Cell Death Is Increased in Mouse Epithelial Cells Infected With Chlamydia muridarum

JOURNAL OF INFECTIOUS DISEASES, 224, S47–S55.

By: U. Nagarajan*, C. Cho*, C. Gyorke*, S. Nagarajan*, J. Ezzell*, H. Brochu n, I. Huntress n, E. Harrell n, X. Peng n

co-author countries: United States of America 🇺🇸
author keywords: Chlamydia muridarum; IL-1 alpha; mouse epithelial cells; mouse model; TNF alpha
MeSH headings : Animals; Cell Death; Chlamydia Infections / immunology; Chlamydia Infections / metabolism; Chlamydia muridarum / immunology; Epithelial Cells; Female; Interleukin-1alpha / immunology; Interleukin-1alpha / metabolism; Mice; Mice, Inbred C57BL; Tumor Necrosis Factor-alpha / immunology; Tumor Necrosis Factor-alpha / metabolism
Source: Web Of Science
Added: September 13, 2021

Abstract Chlamydia trachomatis-genital infection in women can be modeled in mice using Chlamydia muridarum. Using this model, it has been shown that the cytokines tumor necrosis factor (TNF)α and interleukin (IL)-1α lead to irreversible tissue damage in the oviducts. In this study, we investigated the contribution of TNFα on IL-1α synthesis in infected epithelial cells. We show that C muridarum infection enhanced TNFα-induced IL-1α expression and release in a mouse epithelial cell line. In addition to IL-1α, several TNFα-induced inflammatory genes were also highly induced, and infection enhanced TNF-induced cell death. In the mouse model of genital infection, oviducts from mice lacking the TNFα receptor displayed minimal staining for IL-1α compared with wild-type oviducts. Our results suggest TNFα and IL-1α enhance each other’s downstream effects resulting in a hyperinflammatory response to chlamydial infection. We propose that biologics targeting TNF-induced IL-1α synthesis could be used to mitigate tissue damage during chlamydial infection.