Social stress-induced priming of innate immunity is associated with translocation of commensal lactobacilli to the spleen

Abstract

Abstract Exposure to the social disruption (SDR) stressor, which involves repeated social defeat in subordinate mice, increases serum cytokine levels, results in accumulation of CD11b+ myeloid cells in the spleen, and primes macrophages for increased cytokine and microbicidal activity. Our previous studies showed that the intestinal microbiota are necessary for SDR-enhancement of splenic macrophage microbicidal activity. The current study determined whether SDR-induced translocation of microbes to the spleen was associated with changes in spleen myeloid cell populations and cytokine mRNA. The SDR stressor increased the numbers of spleen neutrophils and inflammatory monocytes compared to control mice, while having no effect on numbers of non-classical monocytes and red pulp macrophages. Using an RNA flow cytometry assay, we found that neutrophils and inflammatory monocytes from SDR mice express higher levels of IL-1β mRNA compared to control mice. To detect translocated bacteria, qRT-PCR was used with bacterial group specific primers to 16S rRNA in addition to traditional bacterial cultures. SDR induced the translocation of Lactobacillus to the spleen, but translocation of other taxa, such as Bacteroides and Bifidobacterium, was not increased in stressor-exposed mice. Levels of Lactobacillus 16s rRNA in the spleen positively correlated with increased levels of IL-1β and IL-23 mRNA in stressor-exposed mice. Our results indicate that stressor exposure increases translocation of Lactobacillus from the gut to the spleen and primes the innate immune system for enhanced reactivity. These studies suggest that commensal microbes are key players in stressor-induced immunopotentiation. Funded by NIH grant R21AI107238.