Suppressor of Cytokine Signaling (SOCS) 1 Regulates IFN-γ Signaling in Chlamydia muridarum-Stimulated Mouse Macrophages
Board Location: #3
Discipline: Biological Sciences
Subcategory: Cell and Molecular Biology
Session: 1
Vanella Tadjuidje - Alabama State University
Co-Author(s): Rajnish Sahu, Alabama State University, Montgomery, ALAguy C. Nguiakam Sipower, Alabama State University, Montgomery, ALShree R. Singh, Alabama State University, Montgomery, ALVida A. Dennis, Alabama State University, Montgomery, AL
Chlamydia trachomatis (Ct) is an obligate intracellular bacterium and is the most frequently reported bacterial sexually transmitted infection in the United States. Ct infections often induce inflammation, a mechanism that can increase the survival of the bacterium if left untreated. There is limited natural immunity to Ct, and repeated infections further enhance inflammatory responses. Interferon-gamma (IFN-γ) is a cytokine that regulates macrophage activation via the Janus kinase (JAK)/signal transducer and activators of transcription (STAT) pathway, which can lead to the induction of other pro-inflammatory cytokines. Under normal circumstances, IFN-γ signaling is short-lived to recover homeostasis in the organism. Suppressors of cytokine signaling (SOCS) proteins have been implicated as negative regulators for various inflammatory cytokines by inhibiting the JAK/STAT signaling pathway. We have previously shown that Chlamydia induces the expression of SOCS 1 and SOCS 3, suggesting that Ct may regulate cytokine signaling to control its own inflammation and promote its survival in the host. In this current study, we investigated the role of SOCS 1 induced by Chlamydia and its major outer membrane protein (MOMP) on IFN-γ signaling required for macrophage activation. We hypothesize that Ct inhibits IFN-γ signaling through STAT1 phosphorylation via SOCS1 expression to minimize macrophage activation and its function. We used murine RAW 264.7 macrophages and stimulated them with IFN-γ, murine live C. muridarum, and MOMP. After 24 hours, the cells were stimulated with and without added IFN-γ. Our results show that Chlamydia induced the pro-inflammatory cytokines (IL-6, TNF-α) in macrophages, which were then further enhanced by adding IFN-γ in comparison to the absence of exogenous IFN-γ. The MOMP-stimulated cells producing IL-6 and TNF-α in the presence of exogenous IFN-γ were not altered drastically. We conclude that Chlamydia does inhibit the IFN-γ signaling pathway, thus also inhibiting macrophage activation and its function to promote survival in the host. For future studies, we plan to examine the differences in how Chlamydia and MOMP interact with and affect the IFN-γ signaling pathway.
Funder Acknowledgement(s): The National Science Foundation (NSF) HBCU-UP (HRD-1911660), (NSF)-CREST (HRD-1241701), NSF-HBCU-RISE (HRD-1646729)National Institute of Allergy And Infectious Diseases of the National Institutes of Health under Award Number R21AI111159 and NIH-NIGMS-RISE (1R25GM106995-01)
Faculty Advisor: Vida A. Dennis, vdennis@alasu.edu
Role: I was the sole contributor to this research, as it was a project handed to me by my mentor. I worked on this research from the beginning to the end: I grew, subcultured, and stimulated the cells; I prepared all the stimulants; I collected and tested all the samples to get the results I aimed to present. While I did have help from labmates and my lab supervisor, I contributed the most to this particular research topic.