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Innate immune responses to HIV-1 and Chlamydia trachomatis in the human female reproductive tract / by Lucy Rudo Mukura.

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Author	Mukura, Lucy Rudo.
Title	Innate immune responses to HIV-1 and Chlamydia trachomatis in the human female reproductive tract / by Lucy Rudo Mukura.
Date	2013
Abstract	Female reproductive tract (FRT) secretions contain a spectrum of cytokines, chemokines and antimicrobials that inhibit infection of target cells by HIV-1 and other sexually transmitted pathogens. Innate immune protection maintained by the presence of FRT secretions is compromised by HIV-1 and Chlamydia trachomatis infection. Using cervical-vaginal lavage (CVL) from HIV-1 positive women we demonstrate the impact of genital tract viral load (GTVL) on cytokine/antimicrobial levels. In separate studies, we report the effect of Chlamydia on uterine epithelial cell (UEC) cytokine/chemokine and antimicrobial secretion. CVL were collected from 19 HIV-1 positive women who where not on antiretroviral therapy. The women were catagorized into those with detectable GTVL or those with undetectable GTVL (detectable GTVL RNA levels>400 copies/ml). TZM-bl assay was used to determine the presence of infectious virus and anti-HIV activity. Higher levels of RANTES, Eotaxin, Fractalkine, Il-l[alpha], IL-6, MCP-1, MIP1[Beta], MIP1[alpha], TNF[alpha] and GM-CSF were observed in women with detectable GTVL compared to women with undetectable GTVL. We did not recover any infectious virus and did not find any anti-HIV activity in CVL. UEC constitutively secrete or can be induced to secrete increased amounts of cytokines/chemokines by pattern recognition receptor ligands. Using ECC-1 cells (a human uterine epithelial cell line) and primary UEC, we hypothesized that C. trachomatis infection increases cytokine/chemokine and antimicrobial secretion. ECC-1 cells and primary UEC secreted increased IL-8 and decreased MCP-1 in response to C. trachomatis. HBD2 and trappin-2/elafin secretion by ECC-1 incubated with C. trachomatis was suppressed. In primary UEC, IL-6 and MIP3[alpha] secretion were both inhibited at a high dose of Chlamydia. However, at a low does we observed an increase in MIP3[alpha] secretion by UEC. As part of these studies we found that transepithelial resistance, a measure of epithelial barrier integrity, was decreased in pola
Description	xviii, 206 leaves : ill. (some col.) 28 cm.
Format	application/pdf
Advisor	Charles R. Wira, Paul M. Guyre, Timothy P. Lahey, Susan Cu-Uvin
College	Dartmouth Medical School."
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.992

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Innate immune responses to HIV-1 and Chlamydia trachomatis in the human female reproductive tract / by Lucy Rudo Mukura.

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