Wilbert A. Derbigny, Ph.D.
Associate Professor of Microbiology and Immunology

(317) 955-6252
wderbigny@marian.edu
Evans Center, Room 318B

Wilbert A. Derbigny, Ph.D.

Clinical/Research Interests

Chlamydia trachomatis is a gram-negative intracellular bacterium and the cause of the disease chlamydia, which is the most common sexually transmitted infection in the United States, with over 1.7 million cases reported in the US in 2017 alone. C. trachomatis infections can be effectively treated with antibiotics, but these infections are often asymptomatic and unrecognized in women. To effectively intervene in women where this chronic condition is often discovered late, we need to understand better the mechanisms that lead to pelvic inflammatory disease (PID) and infertility caused during prolonged Chlamydia infection. Our discovery of an unexpected and atypical activation of Toll-like receptor 3 (TLR3) provides exciting new opportunities to better understand chlamydia-related chronic inflammation.

My long-term goal is to understand further the pathophysiologic processes that contribute to Chlamydia-induced reproductive tract pathology. My lab focused on identifying the inflammatory mediators that induce scarring of the oviduct epithelium and identifying therapeutic countermeasures that can prevent this. We were the first to demonstrate (and others have now confirmed) that TLR3 is a key pattern recognition receptor (PRR) in the immune response to Chlamydia muridarum (Cm) infection in mice. We were the first to show that chlamydial induction of IFN-β is TLR3-dependent in oviduct tissue, TLR3-modulates inflammatory immune responses to Chlamydia in vitro, and TLR3-deficient mice develop significantly more chronic inflammatory uterine and oviduct pathology paralleling the human sequelae of untreated chlamydia infection. This set of observations is paradoxical because Cm lacks a known dsRNA agonist for the TLR3 receptor, suggesting that our understanding of TLR3 is incomplete.

The overall objectives of my continuing research program will be: (A) to investigate further the specific cellular pathways and mechanisms that are dysregulated during TLR3 deficiency that contributes to genital tract pathology during Chlamydia infection, (B) to ascertain the specific role (if any) that TLR3 and its effector pathways have on chronic inflammatory genital tract chlamydial disease and persistent infection, and (C) identifying the likely novel chlamydial pathogen-associated molecular pattern (PAMP) that binds to and triggers TLR3 signaling pathways. Because we recently reported that TLR3 deficiency leads to an increased rate of the ascension of Cm into the upper genital tracts of mice and a more rapid breakdown in epithelial barrier function, our data suggest that TLR3 has a role in limiting the chlamydial spread and that TLR3 modulates the chlamydial caused disruption in epithelial barrier function. The chlamydial caused breakdown in the protective epithelial barrier can make the host more vulnerable to co-infection by other sexually transmitted pathogens such as HIV and HPV. The finding that TLR3 can potentially have an impact on limiting the co-infectivity and disease progression of other genital tract pathogens that are commonly observed as a co-infection in patients allows us to expand the scope of our research and pursue other funding sources. In this regard, we hypothesize that Chlamydia causes a breakdown in epithelial barrier function that is partially modulated by TLR3, and the barrier disruption will allow better access to the underlying basal cell layers and thus increasing the infectivity of HPV. Testing this hypothesis will now enable us to pursue funding sources from institutes that fund cancer research as we propose (D) to examine the putative impact that TLR3 has on facilitating cervical carcinogenesis in Chlamydia-HPV co-infected patients.

Current Funding:

NIH – National Institutes of Allergy and Infectious Disease: “Developing a mouse model to examine the specific impact of IFNα in the pathogenesis of genital tract Chlamydia infection (1R03AI154033; starts 8/1/2020).

Recent Publications:

Xu, J. Z., Kumar, R., Gong, H., Liu, L., Ramos-Solis, N., Li, Y., and W. A. Derbigny. (2019). Toll-Like Receptor 3 Deficiency Leads to Altered Immune Responses to Chlamydia trachomatis Infection in Human Oviduct Epithelial Cells. Infect Immun. 87: e00483-19. https://doi.org/10.1128/IAI .00483-19. 

Kumar, R., Gong, H., Liu, L., Ramos-Solis, N., Seye, C., and W. A. Derbigny. (2019). TLR3 Deficiency Exacerbates the Loss of Epithelial Barrier Function during Genital Tract Chlamydia muridarum Infection. PLoS ONE 14(1): e0207422. https://doi.org/10.1371/journal.pone.0207422.

Kumar, R. and W. A. Derbigny. (2018). Cellulose Acetate Electrophoresis of Hemoglobin. Methods Mol Biol. 2019;1855:81-85. doi: 10.1007/978-1-4939-8793-1_7.

Kumar, R. and W. A. Derbigny. (2018). TLR3 Deficiency Leads to a Dysregulation in the Global Gene-Expression Profile of Murine Oviduct Epithelial Cells Infected with Chlamydia muridarum. Madridge J Bioinform Syst Biol.2018; 1(1): 1-13.doi: 10.18689/ijmr-1000101

Carrasco, S, Hu, S., Imai, D. M., Kumar, R., Sandusky, G. E., Yang, X. F., and W.A. Derbigny. (2018). Toll-like receptor 3 (TLR3) Promotes the Resolution of Chlamydia muridarum Genital Tract Infection in Congenic C57BL/6N Mice. PLoS One. 2018 Apr 6;13(4):e0195165. doi: 10.1371/journal.pone.0195165. eCollection 2018. PMID:29624589.

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