1. Experimental bacterial dysbiosis with consequent immune alterations increase intrarectal SIV acquisition susceptibility.
- Author
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Ortiz AM, Baker PJ, Langner CA, Simpson J, Stacy A, Flynn JK, Starke CE, Vinton CL, Fennessey CM, Belkaid Y, Keele BF, and Brenchley JM
- Subjects
- Animals, Macaca mulatta, Vancomycin, Anti-Bacterial Agents, Dysbiosis, Simian Immunodeficiency Virus
- 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 (T
H 17) and TH 22 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., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)- Published
- 2023
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