Project description:The microbiota plays a fundamental role in regulating host immunity. However, the processes that initiate homeostatic immunity to the microbiota remain largely unknown. Here, we show that the skin microbiota promotes the discrete expression of defined endogenous retrovirus (ERVs). Keratinocyte-intrinsic responses to ERVs depended on cGAS/STING signaling and promoted the induction commensal specific T cells including CD8+, CD4+ and MAIT cells. Inhibition of reverse transcriptase significantly impacted these responses resulting in impaired homeostatic immunity to the microbiota and associated tissue repair function. Conversely, diets that caused an increase in dietary lipids primed the skin for aberrant ERV expression in response to commensal colonization, leading to tissue inflammation. Together, our results support the idea that the host may have coopted its endogenous virome as a means to communicate with the exogenous microbial microbiota, resulting in a multikingdom dialogue that controls both tissue homeostasis and inflammation.
Project description:The microbiota plays a fundamental role in regulating host immunity. However, the processes that initiate homeostatic immunity to the microbiota remain largely unknown. Here, we show that the skin microbiota promotes the discrete expression of defined endogenous retrovirus (ERVs). Keratinocyte-intrinsic responses to ERVs depended on cGAS/STING signaling and promoted the induction commensal specific T cells including CD8+, CD4+ and MAIT cells. Inhibition of reverse transcriptase significantly impacted these responses resulting in impaired homeostatic immunity to the microbiota and associated tissue repair function. Conversely, diets that caused an increase in dietary lipids primed the skin for aberrant ERV expression in response to commensal colonization, leading to tissue inflammation. Together, our results support the idea that the host may have coopted its endogenous virome as a means to communicate with the exogenous microbial microbiota, resulting in a multikingdom dialogue that controls both tissue homeostasis and inflammation.
Project description:How the homeostatic dialogue between the host and its microbiota is initiated remains largely unknown. Here, we show that immune response to the skin microbiota is dependent on activity of endogenous retroviruses. Notably, response to the microbiota promotes a discrete transcriptional induction of retroelements. As such, keratinocyte intrinsic sensing of endogenous retrovirus (ERV) derived DNA via cGAS/STING promotes the induction of commensal specific T cells including CD8+, CD4+ and MAIT cells. Consequently, inhibition of reverse transcriptase activity impairs both homeostatic immunity to the microbiota and associated tissue repair function. On the other hand, altered diet and in particular increase in dietary lipids primed the skin for aberrant ERV expression in the context of microbiota exposure leading to tissue inflammation. Together our results support the idea that the host may have coopted its endogenous virome as a means to communicate with exogenous microbiota resulting in a multikingdom dialogue that controls both tissue homeostasis and inflammation.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
Project description:We inflicted TBI to chemokine-deficient mouse lines in order to establish involvement of various signalling pathways that may be addressed therapeutically. Interacting chemokine pathways in brain regulate distinct inflammatory cells. Activated microglia are separate from invading phagocytes and dendritic cells. Findings show potential targets to interfere with specific inflammatory responses after brain injury.
