Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells

HIV的补体调理作用影响人类结直肠黏膜的原发感染以及随后的T细胞活化。

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作者:Pradyot Bhattacharya ,Rada Ellegård ,Mohammad Khalid ,Cecilia Svanberg ,Melissa Govender ,Åsa V Keita ,Johan D Söderholm ,Pär Myrelid ,Esaki M Shankar # ,Sofia Nyström # ,Marie Larsson

Abstract

HIV transmission via genital and colorectal mucosa are the most common routes of dissemination. Here, we explored the effects of free and complement-opsonized HIV on colorectal tissue. Initially, there was higher antiviral responses in the free HIV compared to complement-opsonized virus. The mucosal transcriptional response at 24 hr revealed the involvement of activated T cells, which was mirrored in cellular responses observed at 96 hr in isolated mucosal T cells. Further, HIV exposure led to skewing of T cell phenotypes predominantly to inflammatory CD4+ T cells, that is Th17 and Th1Th17 subsets. Of note, HIV exposure created an environment that altered the CD8+ T cell phenotype, for example expression of regulatory factors, especially when the virions were opsonized with complement factors. Our findings suggest that HIV-opsonization alters the activation and signaling pathways in the colorectal mucosa, which promotes viral establishment by creating an environment that stimulates mucosal T cell activation and inflammatory Th cells.

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