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Nyla Dil 1 (DVM, MSc (Path), PhD)

G enital epithelial cells from HIV-exposed seronegative (HESN) commercial sex workers express a discrete cytokine/chemokines profile upon toll-like receptor activation. Nyla Dil 1 (DVM, MSc (Path), PhD) Joshua Kimani 2 , Makobu Kimani 2 , Francis A. Plummer 1 , T. Blake Ball 1

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Nyla Dil 1 (DVM, MSc (Path), PhD)

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  1. Genital epithelial cells from HIV-exposed seronegative (HESN) commercial sex workers express a discrete cytokine/chemokines profile upon toll-like receptor activation Nyla Dil1(DVM, MSc (Path), PhD) Joshua Kimani2, Makobu Kimani2, Francis A. Plummer1, T. Blake Ball1 1Department of Medical Microbiology and Infectious Diseases, University of Manitoba & Public Health Agency of Canada, Winnipeg, Manitoba, Canada; 2Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya

  2. Background • Most HIV-1 infections acquired through heterosexual transmission across female genital mucosa. • Epithelial cells lining genital mucosa (GECs) act as first line of defense against mucosal infections. • Immune locale orchestrated by TLR mediated activation of GECs can be a critical determinant of HIV-1 infection. Question • What is the role of GECs and TLR signaling in GECs in determining the local mucosal cytokine /chemokines milieu in HIV resistant and susceptible women? Methods • Endocervicalcytobrush samples from PumwaniCSWs cohort ( HESN (n=22), HIV- (n=24) and HIV infected (n=23). • GECs purified through a series of nylon membrane filtrations • Cytokine levels in 24 h culture (with or without 25 ug/ml Poly(I:C), or 1ug/ml Pam3CSK4, 1ug/ml LPS, 100 ng/ml Flagellin and 100ng/ml FSL-1 combined) supernatants using the Milliplex MAP multiplex Human Assay. • TLR expression GEC cell lines from different FGT anatomical sites

  3. TLR and other PRR Expression in GECs TLR 7 and TLR 8 not expressed

  4. IL-8 and IP-10 Production in GECs • HESN GECs show • lower levels of • proinflammatory IL-8 • in response to TLR • stimulation. • HESN GECs show • lower levels of activated • T cell chemoattractant • IP-10 in response to • TLR stimulation.

  5. Conclusions • HESN GECs produce lower levels of basal and TLR mediated IL-8 and IP-10 that may be critical at reducing trafficking to this crucial mucosal site and hence contributing to HIV-1 resistance. • This distinct pattern of mucosal epithelial derived chemokine/cytokine expression contributes to the immune quiescence phenotype observed in the Pumwani HESN cohort. Acknowledgements • Dr. Blake Ball • Dr. Frank Plummer • Dr. Joshua Kimani • Dr. Makobu Kimani • Pumwani CSW Cohort participants

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