title: Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events.
abstract: Chlamydia trachomatis causes a predominantly asymptomatic, but generally inflammatory, genital infection that is associated with an increased risk for HIV acquisition. Endocervical epithelial cells provide the major niche for this obligate intracellular bacterium in women, and the endocervix is also a tissue in which HIV transmission can occur. The mechanism by which CT infection enhances HIV susceptibility at this site, however, is not well understood. Utilizing the A2EN immortalized endocervical epithelial cell line grown on cell culture inserts, we evaluated the direct role that CT-infected epithelial cells play in facilitating HIV transmission events. We determined that CT infection significantly enhanced the apical-to-basolateral migration of cell-associated, but not cell-free, HIVBaL, a CCR5-tropic strain of virus, across the endocervical epithelial barrier. We also established that basolateral supernatants from CT-infected A2EN cells significantly enhanced HIV replication in peripheral mononuclear cells and a CCR5+ T cell line. These results suggest that CT infection of endocervical epithelial cells could facilitate both HIV crossing the mucosal barrier and subsequent infection or replication in underlying target cells. Our studies provide a mechanism by which this common STI could potentially promote the establishment of founder virus populations and the maintenance of local HIV reservoirs in the endocervix. Development of an HIV/STI co-infection model also provides a tool to further explore the role of other sexually transmitted infections in enhancing HIV acquisition.
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, United States of America.
authors.forename: Lyndsey R
authors.initials: LR
authors.lastname: Buckner
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, United States of America.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Amedee
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, United States of America.
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Albritton
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, United States of America.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Kozlowski
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, United States of America.
authors.forename: Nedra
authors.initials: N
authors.lastname: Lacour
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, United States of America.|Department of Medicine, Section of Infectious Diseases, Louisiana State University Health Sciences Center, New Orleans, Louisiana, 70112, United States of America.
authors.forename: Chris L
authors.initials: CL
authors.lastname: McGowin
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, MO 65201, United States of America.
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Schust
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, United States of America.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Quayle
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000382:microbiology / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology; D002692:Chlamydia trachomatis / Q000502:physiology*; D060085:Coinfection / Q000382:microbiology / Q000821:virology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004847:Epithelial Cells / Q000382:microbiology* / Q000821:virology*; D005260:Female; D006678:HIV / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000382:microbiology / Q000821:virology; D056265:Microbial Interactions; D008954:Models, Biological; D019713:Receptors, CCR5 / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
chemical_list: C584933:CCR5 protein, human; D017077:Culture Media, Conditioned; D019713:Receptors, CCR5