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Individual Members of the Microbiota Disproportionately Modulate Host Innate Immune Responses.

ABSTRACT: Predicting host health status based on microbial community structure is a major goal of microbiome research. An implicit assumption of microbiome profiling for diagnostic purposes is that the proportional representation of different taxa determine host phenotypes. To test this assumption, we colonized gnotobiotic zebrafish with zebrafish-derived bacterial isolates and measured bacterial abundance and host neutrophil responses. Surprisingly, combinations of bacteria elicited immune responses that do not reflect the numerically dominant species. These data are consistent with a quantitative model in which the host responses to commensal species are additive but where various species have different per capita immunostimulatory effects. For example, one species has a high per capita immunosuppression that is mediated through a potent secreted factor. We conclude that the proportional representation of bacteria in a community does not necessarily predict its functional capacities; however, characterizing specific properties of individual species offers predictive insights into multi-species community function.

SUBMITTER: Rolig AS

PROVIDER: S-EPMC4701053 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Individual Members of the Microbiota Disproportionately Modulate Host Innate Immune Responses.

Rolig Annah S AS Parthasarathy Raghuveer R Burns Adam R AR Bohannan Brendan J M BJ Guillemin Karen K

Cell host & microbe 20151101 5

Predicting host health status based on microbial community structure is a major goal of microbiome research. An implicit assumption of microbiome profiling for diagnostic purposes is that the proportional representation of different taxa determine host phenotypes. To test this assumption, we colonized gnotobiotic zebrafish with zebrafish-derived bacterial isolates and measured bacterial abundance and host neutrophil responses. Surprisingly, combinations of bacteria elicited immune responses that ...[more]

PMID: 26567512

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Project description:Prevalence of the members of herpesvirus family in oral inflammatory diseases is increasingly acknowledged suggesting their likely role as an etiological factor. However, the underlying mechanisms remain obscure. In our recent miRNA profiling of healthy and diseased human tooth pulps, elevated expression of human herpesvirus encoded viral microRNAs (v-miRs) were identified. Based on the fold induction and significance values, we selected three v-miRs namely miR-K12-3-3p [Kaposi sarcoma-associated virus (KSHV)], miR-H1 [herpes simplex virus 1 (HSV1)], and miR-UL-70-3p [human cytomegalovirus (HCMV)] to further examine their impact on host cellular functions. We examined their impact on cellular miRNA profiles of primary human oral keratinocytes (HOK). Our results show differential expression of several host miRNAs in v-miR-transfected HOK. High levels of v-miRs were detected in exosomes derived from v-miR transfected HOK as well as the KSHV-infected cell lines. We show that HOK-derived exosomes release their contents into macrophages (M?) and alter expression of endogenous miRNAs. Concurrent expression analysis of precursor (pre)-miRNA and mature miRNA suggest transcriptional or posttranscriptional impact of v-miRs on the cellular miRNAs. Employing bioinformatics, we predicted several pathways targeted by deregulated cellular miRNAs that include cytoskeletal organization, endocytosis, and cellular signaling. We validated three novel targets of miR-K12-3-3p and miR-H1 that are involved in endocytic and intracellular trafficking pathways. To evaluate the functional consequence of this regulation, we performed phagocytic uptake of labeled bacteria and noticed significant attenuation in miR-H1 and miR-K12-3-3p but not miR-UL70-3p transfected primary human M?. Multiple cytokine analysis of E. coli challenged M? revealed marked reduction of secreted cytokine levels with important roles in innate and adaptive immune responses suggesting a role of v-miRs in immune subversion. Our findings reveal that oral disease associated v-miRs can dysregulate functions of key host cells that shape oral mucosal immunity thus exacerbating disease severity and progression.

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Individual Members of the Microbiota Disproportionately Modulate Host Innate Immune Responses.

Publications

Individual Members of the Microbiota Disproportionately Modulate Host Innate Immune Responses.

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