Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.
Inserm Unit 976, Hôpital Saint-Louis, 75010 Paris, France.
Proc Natl Acad Sci U S A. 2020 Jul 14;117(28):16465-16474. doi: 10.1073/pnas.2003022117. Epub 2020 Jun 29.
Under steady-state conditions, the immune system is poised to sense and respond to the microbiota. As such, immunity to the microbiota, including T cell responses, is expected to precede any inflammatory trigger. How this pool of preformed microbiota-specific T cells contributes to tissue pathologies remains unclear. Here, using an experimental model of psoriasis, we show that recall responses to commensal skin fungi can significantly aggravate tissue inflammation. Enhanced pathology caused by fungi preexposure depends on Th17 responses and neutrophil extracellular traps and recapitulates features of the transcriptional landscape of human lesional psoriatic skin. Together, our results propose that recall responses directed to skin fungi can directly promote skin inflammation and that exploration of tissue inflammation should be assessed in the context of recall responses to the microbiota.
在稳态条件下，免疫系统随时准备感知和响应微生物组。因此，对微生物组的免疫，包括 T 细胞反应，预计将先于任何炎症触发。然而，这些预先形成的微生物组特异性 T 细胞如何导致组织病理学仍不清楚。在这里，我们使用银屑病的实验模型表明，对共生皮肤真菌的回忆反应会显著加重组织炎症。真菌预先暴露引起的增强病理学依赖于 Th17 反应和中性粒细胞细胞外陷阱，并且再现了人类病变银屑病皮肤转录景观的特征。总之，我们的结果表明，针对皮肤真菌的回忆反应可以直接促进皮肤炎症，并且应该在回忆反应到微生物组的背景下评估组织炎症。
