| Autor: |
Farias Amorim, Camila, Lovins, Victoria M., Singh, Tej Pratap, Novais, Fernanda O., Harris, Jordan C., Lago, Alexsandro S., Carvalho, Lucas P., Carvalho, Edgar M., Beiting, Daniel P., Scott, Phillip, Grice, Elizabeth A. |
| Zdroj: |
Science Translational Medicine; 10/18/2023, Vol. 15 Issue 718, p1-14, 14p |
| Abstrakt: |
Leishmania braziliensis is a parasitic infection that can result 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 patients infected with L. braziliensis. 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. Quantification of host and bacterial transcripts on 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 outcomes in L. braziliensis–infected mice colonized with S. aureus, given that its neutralization reduced pathology and inflammation. These results highlight how the human microbiome can shape disease outcomes in cutaneous leishmaniasis and suggest pathways toward host-directed therapies to mitigate the inflammatory consequences. Editor's summary: Leishmaniasis is a zoonotic parasitic infection transmitted to humans through the bite of sandflies and can manifest in several forms, including cutaneous leishmaniasis. Farias Amorim et al. examined the influence of the skin microbiome on disease outcomes of 62 patients infected with Leishmania braziliensis. Larger skin microbial burdens and overrepresentation of Staphylococcus spp. correlated with slower healing of cutaneous leishmaniasis lesions. Analysis of host and microbial transcripts revealed that lesions enriched for Staphylococcus aureus expressed more inflammatory markers, especially IL-1β family members. They verified that cutaneous IL-1β delayed lesion healing in mice colonized with S. aureus and infected with L. braziliensis. These findings reveal the influence that skin microbiota can have on the resolution of cutaneous leishmaniasis and highlight IL-1β as a potential immunotherapy target for cutaneous leishmaniasis. -Christiana N. Fogg [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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