3061-Derbigny, Wilbert

Wilbert A. Derbigny, PhD

Adjunct Associate Professor of Microbiology & Immunology

MS 420
635 Barnhill Drive

Indianapolis, IN

Titles & Appointments

  • Adjunct Associate Professor of Microbiology & Immunology
  • Education
    2001 PhD Louisiana State University
    1990 BS Xavier University of Louisiana
  • Research

    Chlamydia trachomatis infections are major causes of several sexually transmitted diseases and are prevalent in both industrialized and developing countries.   The epithelial cells lining the reproductive tract are the major cell type productively infected with C. trachomatis, and the emphasis of our research will be to investigate the contribution of the infected epithelial cells to host defense. 

    The focus of our studies involves defining the precise regulation of the specific cell signaling pathways that are activated during Chlamydia infection.  To better understand the molecular cascade of events that ensues upon infection with C. trachomatis, a non-transformed murine oviduct epithelial cell line was developed using cells lining the oviduct epithelium of B6 mice.  Our early work showed that the oviduct epithelial cell lines expressed mRNA for TLR1,-2, -3, -5, and -6, but failed to express any mRNA for TLR4, -7, -8, and -9.  Additionally, we showed that these cells expressed mRNA for other pattern recognition receptors (PRRs) including Nod1 and Nod2.  Experiments utilizing si-RNA and dominant-negative proteins showed that secretion of the acute inflammatory cytokines IL-6 and GM-CSF by Chlamydia-infected oviduct epithelial cells was dependent on TLR2 and MyD88.

    An interesting finding from this early work demonstrated that infection of the oviduct epithelial cells with C. muridarum, a mouse homolog of the human pathogen C. trachomatis, resulted in significant levels of interferon beta (IFN-β) production that was independent of MyD88; a major component in the TLR-signaling pathways.  We recently showed in a follow-up manuscript that the IFN-β that was produced during infection was largely dependent upon TRIF and IRF-3, two major signaling components found in the TLR3 signaling pathway.  Although the oviduct epithelial cells expressed TLR3 mRNA, they were unresponsive to extracellular poly (I:C) (a potent TLR3 agonist), and to date there are no known components in Chlamydia that has been demonstrated to be an effective stimulator of TLR3.  However, our data implicated TLR3 or an unknown PRM as the PRM responsible for IFN-β production, and we plan to further investigate the role of TLR3 and to define the exact component of the Chlamydia structure that serves as an agonist for IFN-β production during infection of oviduct epithelial cells.

    A second major component of our research interests will focus on the effect(s) that IFN-β has on the regulation of IL-12p70, and other chemokines including Rantes, IP-10 (CXCL10), CXCL16, and MIG (CXCL9) theorized to preferentially recruit Th1 lymphocytes to the upper genital tract during Chlamydia infection.  It has been previously demonstrated that Chlamydia-infected oviduct epithelial cells expressed mRNA for both the IL-12p35 and IL-12p40 chains of the IL-12p70 heterodimer, and that C. muridaruminfection of the oviduct epithelial cell-lines produced considerable levels of many different types of chemokines involved in leukocyte recruitment such as CXCL1, Rantes and MIP2.  The discovery that oviduct epithelial cells express both IFN-β and IL-12p70 in response to C. muridarum infection implies that epithelial cells play a role in immune regulation at mucosal surfaces.  Our research interest(s) in this particular project is based on the hypothesis that infected-epithelial cell production of IFN-β regulates epithelial IL-12p70, Rantes, IP-10 (CXCL10), CXCL16, and MIG (CXCL9) secretion, and that this regulatory pathway plays an important role in local immune responses within reproductive tract mucosa and is a critical step in host immunity to Chlamydia infections.


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