The skin microbiome enhances disease through IL-1b and delays healing in cutaneous leishmaniasis patients.
The skin microbiome enhances disease through IL-1b and delays healing in cutaneous leishmaniasis patients.
复制标题
皮肤微生物群通过 IL-1b 增强疾病并延迟皮肤利什曼病患者的愈合。
DOI：
10.1101/2023.02.02.23285247
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Grice,ElizabethA
中科院分区：
文献类型：
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作者：
FariasAmorim,Camila;Lovins,VictoriaM;Singh,TejPratap;Novais,FernandaO;Harris,JordanC;Lago,AlexsandroS;Carvalho,LucasP;Carvalho,EdgarM;Beiting,DanielP;Scott,Phillip;Grice,ElizabethA
巴西利什曼原虫是一种寄生虫感染，可导致炎症和皮肤损伤，临床结果变化很大且不可预测。在这里，我们通过对 62 名感染李斯特菌的患者的皮肤微生物组和宿主转录组进行综合分析，研究了微生物群对感染引起的炎症反应和疾病消退的潜在影响。巴西人。我们发现总体细菌负荷和微生物组结构以葡萄球菌属为主。与延迟愈合和增强炎症反应有关，尤其是 IL-1 家族成员的炎症反应。对人类病变的宿主和细菌转录本的定量显示，高病变。金黄色葡萄球菌转录丰度与愈合延迟和 IL-1β 表达增加相关。这种细胞因子对于调节 L 疾病结果至关重要。感染巴西丝虫的小鼠定植有巴西丝虫。金黄色葡萄球菌，因为它的中和作用减少了病理和炎症。这些结果强调了人类微生物组如何影响皮肤利什曼病的疾病结果，并提出了减轻炎症后果的宿主导向疗法的途径。
Leishmania braziliensisis 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 withL. braziliensis. We found that overall bacterial burden and microbiome configurations dominated withStaphylococcusspp. 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 lesionalS. aureustranscript abundance was associated with delayed healing and increased expression of IL-1β. This cytokine was critical for modulating disease outcomes inL. braziliensis–infected mice colonized withS. 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.