Kwaku Geneva N, Jensen Kirstine Nolling, Simaku Patricia, Floyd Daniel J, Saelens Joseph W, Reardon Christopher M, Ward Rebecca A, Basham Kyle J, Hepworth Olivia W, Vyas Tammy D, Zamith-Miranda Daniel, Nosanchuk Joshua D, Vyas Jatin M, Harding Hannah Brown
Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
bioRxiv. 2025 Jan 3:2025.01.03.631181. doi: 10.1101/2025.01.03.631181.
Microbial pathogens generate extracellular vesicles (EVs) for intercellular communication and quorum sensing. Microbial EVs also induce inflammatory pathways within host innate immune cells. We previously demonstrated that EVs secreted by trigger type I interferon signaling in host cells specifically via the cGAS-STING innate immune signaling pathway. Here, we show that despite sharing similar properties of morphology and internal DNA content, the interactions between EVs and the innate immune system differ according to the parental fungal species. EVs secreted by , and are endocytosed at different rates by murine macrophages triggering varied cytokine responses, innate immune signaling, and subsequent immune cell recruitment. Notably, cell wall constituents that decorate and EVs inhibit efficient internalization by macrophages and dampen innate immune activation. Our data uncover the transcriptional and functional consequences of the internalization of diverse fungal EVs by immune cells and reveal novel insights into the early innate immune response to distinct clinically significant fungal pathogens.
微生物病原体产生细胞外囊泡（EVs）用于细胞间通讯和群体感应。微生物EVs还可在宿主固有免疫细胞内诱导炎症途径。我们之前证明，由[具体微生物]分泌的EVs通过cGAS-STING固有免疫信号通路在宿主细胞中特异性触发I型干扰素信号传导。在此，我们表明，尽管EVs在形态和内部DNA含量方面具有相似特性，但EVs与固有免疫系统之间的相互作用因亲本真菌种类而异。由[不同真菌种类]分泌的EVs被小鼠巨噬细胞以不同速率内吞，引发不同的细胞因子反应、固有免疫信号传导及随后的免疫细胞募集。值得注意的是，装饰[不同真菌种类]EVs的细胞壁成分会抑制巨噬细胞的有效内化，并减弱固有免疫激活。我们的数据揭示了免疫细胞内化不同真菌EVs的转录和功能后果，并揭示了对不同临床重要真菌病原体早期固有免疫反应的新见解。
