Experimental bacterial dysbiosis with consequent immune alterations increase intrarectal SIV acquisition susceptibility

Cell Rep. 2023 Jan 31;42(1):112020. doi: 10.1016/j.celrep.2023.112020. Epub 2023 Jan 23.

Abstract

Variations in the composition of the intestinal bacterial microbiome correlate with acquisition of some sexually transmitted pathogens. To experimentally assess the contribution of intestinal dysbiosis to rectal lentiviral acquisition, we induce dysbiosis in rhesus macaques (RMs) with the antibiotic vancomycin prior to repeated low-dose intrarectal challenge with simian immunodeficiency virus (SIV) SIVmac239X. Vancomycin administration reduces T helper 17 (TH17) and TH22 frequencies, increases expression of host bacterial sensors and antibacterial peptides, and increases numbers of transmitted-founder (T/F) variants detected upon SIV acquisition. We observe that SIV acquisition does not correlate with measures of dysbiosis but rather associates with perturbations in the host antimicrobial program. These findings establish a functional association between the intestinal microbiome and susceptibility to lentiviral acquisition across the rectal epithelial barrier.

Keywords: CP: Immunology; CP: Microbiology; HIV; SIV; T(H)17; T(H)22; macaque; men who have sex with men; microbiome.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Anti-Bacterial Agents
  • Dysbiosis*
  • Macaca mulatta
  • Simian Immunodeficiency Virus*
  • Vancomycin

Substances

  • Vancomycin
  • Anti-Bacterial Agents