Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis.
Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis.
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DOI：
10.1371/journal.ppat.1009693
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发表时间：
2021-10
期刊：
影响因子：
6.7
通讯作者：
Scott P
中科院分区：
文献类型：
--
作者：
Singh TP;Carvalho AM;Sacramento LA;Grice EA;Scott P
先天性淋巴样细胞（ILC）包括维持屏障功能的免疫细胞的异质群体，并且可以在感染时启动保护性或病理性免疫应答。在这里，我们显示了在皮肤利什曼病的微生物群驱动的免疫病理学的IL-17A产生的ILC的参与。IL-17A产生的ILC是ROR γ t+，并在感染的皮肤中富集，并且在L.严重感染加重了皮肤炎症反应和产生IL-17 A的ROR γ t + ILC积累，而不影响1型免疫反应。ILC中的IL-17A应答由Batf3依赖性CD103+树突细胞和IL-23指导。此外，使用Rag1-/-小鼠的实验确定IL-17 A + ILC足以驱动炎症反应，因为ILC的消耗或IL-17 A的中和减少了微生物群介导的免疫病理学。总之，这项研究表明，皮肤微生物群促进ROR γ t + IL-17 A产生ILC，这增加了皮肤利什曼病的皮肤炎症。皮肤利什曼病包括一系列疾病，从单一的溃疡性病变到严重的转移性病变，疾病的严重程度往往受到与寄生虫负荷无关的因素的影响。这里，使用L.主要感染的小鼠中，我们发现微生物群依赖性IL-17 A分泌ILC在感染后早期促进疾病增加。虽然微生物群驱动的分泌IL-17 A的ILC介导的炎症反应不依赖于寄生虫负荷和1型免疫反应，但它需要刺激Batf3依赖性皮肤树突状细胞，产生IL-23和中性粒细胞的存在。这项研究为微生物群和先天免疫系统如何影响感染L.少校
Innate lymphoid cells (ILCs) comprise a heterogeneous population of immune cells that maintain barrier function and can initiate a protective or pathological immune response upon infection. Here we show the involvement of IL-17A-producing ILCs in microbiota-driven immunopathology in cutaneous leishmaniasis. IL-17A-producing ILCs were RORγt+ and were enriched in Leishmania major infected skin, and topical colonization with Staphylococcus epidermidis before L. major infection exacerbated the skin inflammatory responses and IL-17A-producing RORγt+ ILC accumulation without impacting type 1 immune responses. IL-17A responses in ILCs were directed by Batf3 dependent CD103+ dendritic cells and IL-23. Moreover, experiments using Rag1-/- mice established that IL-17A+ ILCs were sufficient in driving the inflammatory responses as depletion of ILCs or neutralization of IL-17A diminished the microbiota mediated immunopathology. Taken together, this study indicates that the skin microbiota promotes RORγt+ IL-17A-producing ILCs, which augment the skin inflammation in cutaneous leishmaniasis. Cutaneous leishmaniasis includes a spectrum of diseases ranging from a single ulcerative lesion to severe metastatic lesions, and the magnitude of the disease is often influenced by factors that are independent from the parasite burden. Here, using L. major infected mice, we discovered that microbiota-dependent IL-17A–secreting ILCs promote increased disease early after infection. While the microbiota driven IL-17A–secreting ILCs mediated inflammatory response was independent of the parasite burden and a type 1 immune responses, it required stimulation of Batf3-dependent skin dendritic cells, production of IL-23 and the presence of neutrophils. This study provides mechanistic insight into how microbiota and the innate immune system influence pathology early after infection with L. major.
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影响因子：
16.6
作者：
Li Z;Hodgkinson T;Gothard EJ;Boroumand S;Lamb R;Cummins I;Narang P;Sawtell A;Coles J;Leonov G;Reboldi A;Buckley CD;Cupedo T;Siebel C;Bayat A;Coles MC;Ambler CA
通讯作者：
Ambler CA
DOI：
10.1073/pnas.1004204107
发表时间：
2010-08-17
影响因子：
11.1
作者：
Grice, Elizabeth A.;Snitkin, Evan S.;Segre, Julia A.
通讯作者：
Segre, Julia A.
影响因子：
5.4
作者：
Ashok, Devika;Schuster, Steffen;Acha-Orbea, Hans
通讯作者：
Acha-Orbea, Hans
影响因子：
4.3
作者：
Banerjee, Antara;Bhattacharya, Parna;Nakhasi, Hira L.
通讯作者：
Nakhasi, Hira L.
影响因子：
30.5
作者：
Bernink, Jochem H.;Ohne, Yoichiro;Humbles, Alison A.
通讯作者：
Humbles, Alison A.