Dataset Information

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

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.

SUBMITTER: Sui Y

PROVIDER: S-EPMC6030500 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Sui Yongjun Y Dzutsev Amiran A Venzon David D Frey Blake B Thovarai Vishal V Trinchieri Giorgio G Berzofsky Jay A JA

Mucosal immunology 20180601 4

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 r ...[more]

PMID: 29858581

Similar Datasets

Project description:BACKGROUND: Since there is still no protective HIV vaccine available, better insights into immune mechanism of persons effectively controlling HIV replication in the absence of any therapy should contribute to improve further vaccine designs. However, little is known about the mucosal immune response of this small unique group of patients. Using the SIV-macaque-model for AIDS, we had the rare opportunity to analyze 14 SIV-infected rhesus macaques durably controlling viral replication (controllers). We investigated the virological and immunological profile of blood and three different mucosal tissues and compared their data to those of uninfected and animals progressing to AIDS-like disease (progressors). RESULTS: Lymphocytes from blood, bronchoalveolar lavage (BAL), and duodenal and colonic biopsies were phenotypically characterized by polychromatic flow cytometry. In controllers, we observed higher levels of CD4+, CD4+CCR5+ and Gag-specific CD8+ T-cells as well as lower immune activation in blood and all mucosal sites compared to progressors. However, we could also demonstrate that immunological changes are distinct between these three mucosal sites.Intracellular cytokine staining demonstrated a significantly higher systemic and mucosal CD8+ Gag-specific cellular immune response in controllers than in progressors. Most remarkable was the polyfunctional cytokine profile of CD8+ lymphocytes in BAL of controllers, which significantly dominated over their blood response. The overall suppression of viral replication in the controllers was confirmed by almost no detectable viral RNA in blood and all mucosal tissues investigated. CONCLUSION: A strong and complex virus-specific CD8+ T-cell response in blood and especially in mucosal tissue of SIV-infected macaques was associated with low immune activation and an efficient suppression of viral replication. This likely afforded a repopulation of CD4+ T-cells in different mucosal compartments to almost normal levels. We conclude, that a robust SIV-specific mucosal immune response seems to be essential for establishing and maintaining the controller status and consequently for long-term survival.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets