{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T02:11:03Z","timestamp":1772244663884,"version":"3.50.1"},"reference-count":62,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T00:00:00Z","timestamp":1554940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD072693"],"award-info":[{"award-number":["HD072693"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec><jats:title>Problem<\/jats:title><jats:p><jats:italic>Neisseria gonorrhoeae<\/jats:italic> (NG) <jats:italic>infection<\/jats:italic> has been shown to increase sexual transmission of HIV\u20101. However, the mechanism of NG\u2010induced enhanced HIV\u20101 transmission is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>(a) The cervical tissues were exposed to NG, and cytokine induction was monitored by measuring cytokine proteins in culture supernatants and cytokine mRNAs in tissues. (b) Transcription and replication of HIV\u20101 in TZM\u2010bl, U1, and ACH2 cells were measured by Beta\u2010Gal activity and p24 proteins in the supernatant, respectively. (c) HIV\u20101 transmission was assayed in an organ culture system by measuring transmitted HIV\u20101 in supernatant and HIV\u20101 gag mRNA in the tissues. (d) Transcriptome analysis was done using second generation sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>(a) NG induced membrane ruffling of epithelial layer, caused migration of CD3+ cells to the intraepithelial region, and induced high levels of inflammatory cytokines IL\u20101\u03b2 and TNF\u2010\u03b1. (b) NG\u2010induced supernatants (NGIS) increased HIV\u20101 transcription, induced HIV\u20101 from latently infected cells, and increased transmission of HIV\u20101 across cervical mucosa. (c) Transcriptome analysis of the epithelial layer of the tissues exposed to NG, and HIV\u20101 showed significant upregulation of CXCL10 and IL8. IL\u20101\u03b2 increased the induction of CXCL10 and IL\u20108 expression in cervical mucosa with a concomitant increase in HIV\u20101 transmission.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We present a model in which IL\u20101\u03b2 produced from cervical epithelium during NG exposure increases CXCL10 and IL8 in epithelia. This in turn causes upon HIV\u20101 infection, the migration of HIV\u20101 target cells toward the subepithelium, resulting in increased HIV\u20101 transcription in the sub\u2010mucosa and subsequent enhancement of transmission across cervical mucosa.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13111","type":"journal-article","created":{"date-parts":[[2019,3,23]],"date-time":"2019-03-23T13:49:54Z","timestamp":1553348994000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<i>Neisseria gonorrhoeae<\/i> uses cellular proteins CXCL10 and IL8 to enhance HIV\u20101 transmission across cervical mucosa"],"prefix":"10.1111","volume":"81","author":[{"given":"Anwesha","family":"Sanyal","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Microbiology Pittsburgh 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