Plasmacytoid Dendritic Cells Facilitate Th Cell Cytokine Responses throughout Schistosoma mansoni Infection.
Plasmacytoid Dendritic Cells Facilitate Th Cell Cytokine Responses throughout Schistosoma mansoni Infection.
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DOI：
10.4049/immunohorizons.2100071
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发表时间：
2021-08-30
期刊：
影响因子：
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通讯作者：
MacDonald AS
中科院分区：
文献类型：
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作者：
Webb LM;Phythian-Adams AT;Costain AH;Brown SL;Lundie RJ;Forde-Thomas J;Cook PC;Jackson-Jones LH;Marley AK;Smits HH;Hoffmann KF;Tait Wojno ED;MacDonald AS
浆细胞样树突状细胞（pDC）是病毒感染期间I型IFN（IFN-I）的有效生产者，并且在促进其功能的正反馈回路中响应IFN-I。IFN-I在蠕虫感染期间塑造DC应答，影响DC支持Th 2应答的能力。然而，pDC在2型炎症中的作用尚不清楚。先前的研究表明，pDC在小鼠感染曼氏血吸虫的早期阶段，在寄生虫产卵开始时，对肝或脾的Th 2应答是敏感的。然而，在S.在曼氏感染中，需要针对成熟寄生虫卵的持续Th 2应答来保护肝脏和肠免受急性损伤，并且pDC如何参与急性感染以外的各种组织中针对卵和蠕虫的免疫应答仍不清楚。我们现在表明，pDC是响应于S.在整个感染过程中，在腹膜引流肠系膜淋巴结（MLN）中的曼氏虫卵，以及在感染的后期时间点的最佳虫卵特异性IFNγ。此外，慢性感染阶段的pDC消耗导致肝脏和脾脏病理学增加，以及肝脏中Th 2细胞细胞因子产生和活化消失。在体外，MLN pDC支持来自感染经历的CD 4 + T细胞的Th 2细胞应答，该过程依赖于pDC IFN-1应答，但不依赖于抗原。总之，这些数据突出了pDC和IFN-I在蠕虫感染期间维持和加强LN和发炎组织中的2型免疫中的先前未被认识到的作用。
Plasmacytoid dendritic cells (pDCs) are potent producers of Type I IFN (IFN-I) during viral infection and respond to IFN-I in a positive feedback loop that promotes their function. IFN-I shapes DC responses during helminth infection, impacting the ability of DCs to support Th2 responses. However, the role of pDCs in type 2 inflammation is unclear. Previous studies have shown that pDCs are dispensable for hepatic or splenic Th2 responses during the early stages of murine infection with the trematode Schistosoma mansoni, at the onset of parasite egg laying. However, during S. mansoni infection, an ongoing Th2 response against mature parasite eggs is required to protect the liver and intestine from acute damage, and how pDCs participate in immune responses to eggs and adult worms in various tissues beyond acute infection remains unclear. We now show that pDCs are required for optimal Th2 cytokine production in response to S. mansoni eggs in the intestinal-draining mesenteric lymph nodes (MLNs) throughout infection, and for optimal egg-specific IFNγ at later timepoints of infection. Further, pDC depletion at chronic stages of infection led to increased hepatic and splenic pathology, as well as abrogated Th2 cell cytokine production and activation in the liver. In vitro, MLN pDCs supported Th2 cell responses from infection-experienced CD4+ T cells, a process dependent on pDC IFN-I responsiveness, yet independent of antigen. Together, these data highlight a previously unappreciated role for pDCs and IFN-I in maintaining and reinforcing type 2 immunity in the LNs and inflamed tissue during helminth infection.