Tumor Necrosis Factor Alpha-Induced Interleukin-1 Alpha Synthesis and Cell Death Is Increased in Mouse Epithelial Cells Infected With Chlamydia muridarum. (16th August 2021)

• Record Type: Journal Article
• Authors: Nagarajan, Uma M; Cho, Crescentia; Gyorke, Clare E; Nagarajan, Shanmugam; Ezzell, J Ashley; Brochu, Hayden; Huntress, Ian; Harrell, Erin; Peng, Xinxia
• Is Part Of: Journal of infectious diseases. Volume 224:(2021)supplement 2
• Page Start: S47
• Page End: S55
• Publication Date: 2021-08-16
• Subjects: Chlamydia muridarum -- IL-1α -- mouse epithelial cells -- mouse -- model -- TNFα; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiab168
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: C hlamydia 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.