Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells
Document Type
Article
Publication Date
9-1-2020
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 complementopsonized 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.
Keywords
Adolescent, Adult, Colon, Complement Activation, Complement System Proteins, Female, HIV Infections, HIV-1, Humans, Intestinal Mucosa, Lymphocyte Activation, Male, Opsonin Proteins, T-Lymphocytes, Young Adult
Divisions
ceria
Funders
Swedish Physicians against AIDS Research Foundation,National Institute of Allergy and Infectious Diseases [Grant No: R01AI052731],The Swedish International Development Cooperation Agency,SIDA SARC,VINNMER for Vinnova,Linköping University Hospital Research Fund
Publication Title
eLife
Volume
9
Publisher
eLife Sciences Publications
Publisher Location
SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND