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Multi-omic profiling of cutaneous leishmaniasis infections reveals microbiota-driven mechanisms underlying disease severity

ABSTRACT: Leishmania braziliensis infection results in inflammation and skin injury, with highly variable and unpredictable clinical outcomes. Here, we investigated the potential impact of microbiota on infection-induced inflammatory responses and disease resolution by conducting an integrated analysis of the skin microbiome and host transcriptome on a cohort of 62 L. braziliensis-infected patients. We found that overall bacterial burden and microbiome configurations dominated with Staphylococcus spp. were associated with delayed healing and enhanced inflammatory responses, especially by IL-1 family members. Dual RNA-seq of human lesions revealed that high lesional S. aureus transcript abundance was associated with delayed healing and increased expression of IL-1β. This cytokine was critical for modulating disease outcome in L. braziliensis-infected mice colonized with S. aureus, as its neutralization reduced pathology and inflammation. These results implicate the microbiome in cutaneous leishmaniasis disease outcomes in humans and suggest host-directed therapies to mitigate the inflammatory consequences.

ORGANISM(S): Homo sapiens

PROVIDER: GSE214397 | GEO | 2023/07/27

REPOSITORIES: GEO

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