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

Elife. 2020 Sep 2;9:e57869. doi: 10.7554/eLife.57869.

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.

Keywords: HIV; colorectal mucosa; human; infectious disease; innnate responses; microbiology; t lymphocytes; virus infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Colon / immunology
  • Colon / virology
  • Complement Activation / immunology*
  • Complement System Proteins / chemistry
  • Complement System Proteins / immunology
  • Complement System Proteins / metabolism
  • Female
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / virology
  • Lymphocyte Activation / immunology*
  • Male
  • Opsonin Proteins / chemistry
  • Opsonin Proteins / immunology
  • Opsonin Proteins / metabolism
  • T-Lymphocytes / immunology
  • Young Adult

Substances

  • Opsonin Proteins
  • Complement System Proteins

Associated data

  • GEO/GSE149749