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Influence of gut microbiome on mucosal immune activation and SHIV viral transmission in naive macaques

Mucosal Immunology (2018) | Download Citation

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Abstract

It is unknown whether the gut microbiome affects HIV transmission. In our recent SHIV vaccine study, we found that the naive rhesus macaques from two different sources had significantly different rates of infection against repeated low-dose intrarectal challenge with SHIVSF162P4 virus. Exploring causes, we found that the more susceptible group of seven macaques had significantly more activated CD4+CCR5+Ki67+ T cells in the rectal mucosa than the more resistant group of 11 macaques from a different source. The prevalence of pre-challenge activated rectal CD4 T cells in the naive macaques correlated inversely with the number of challenges required to infect. Because the two naive groups came from different sources, we hypothesized that their microbiomes may differ and might explain the activation difference. Indeed, after sequencing 16s rRNA, we found differences between the two naive groups that correlated with immune activation status. Distinct gut microbiota induced different levels of immune activation ex vivo. Significantly lower ratios of Bacteroides to Prevotella, and significantly lower levels of Firmicutes were found in the susceptible cohort, which were also inversely correlated with high levels of immune activation in the rectal mucosa. Thus, host-microbiome interactions might influence HIV/SIV mucosal transmission through effects on mucosal immune activation.

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Author information

Affiliations

  1. Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    • Yongjun Sui
    • , Blake Frey
    •  & Jay A. Berzofsky
  2. Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    • Amiran Dzutsev
    • , Vishal Thovarai
    •  & Giorgio Trinchieri
  3. Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    • David Venzon

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Contributions

Y.S., J.A.B. designed research studies, Y.S., A.D., B.F. conducted experiments, Y.S., A.D. acquired the data, Y.S., D.V., A.D., J.A.B., G.T., and V.T. analyzed the data, Y.S. wrote original draft, and Y.S., J.A.B. wrote the manuscript.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Yongjun Sui or Jay A. Berzofsky.

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https://doi.org/10.1038/s41385-018-0029-0

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