IL-1 Coordinates the Neutrophil Response to C. albicans in the Oral Mucosa.
IL-1 Coordinates the Neutrophil Response to C. albicans in the Oral Mucosa.
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DOI：
10.1371/journal.ppat.1005882
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发表时间：
2016-09
期刊：
影响因子：
6.7
通讯作者：
LeibundGut-Landmann S
中科院分区：
文献类型：
--
作者：
Altmeier S;Toska A;Sparber F;Teijeira A;Halin C;LeibundGut-Landmann S
白色念珠菌引起的粘液菌感染属于最常见的真菌病。宿主保护是由细胞免疫赋予的;然而，抗真菌免疫的诱导还不清楚。使用小鼠模型的口咽念珠菌病（OPC），我们表明，白细胞介素-1受体（IL-1 R）信号是至关重要的真菌控制在感染开始时，通过其影响中性粒细胞在两个层面上。我们证明，无论是招聘循环中性粒细胞的感染部位和动员新产生的中性粒细胞从骨髓依赖于IL-1 R。因此，IL-1 R缺陷小鼠在感染部位表现出趋化因子的产生受损，并且在循环中对C.白色念珠菌。引人注目的是，在OPC过程中，内皮细胞被鉴定为G-CSF的主要细胞来源，G-CSF对感染组织中角质形成细胞释放的IL-1α产生反应。使用一种新的小鼠舌源性角质形成细胞系和一种已建立的内皮细胞系，在体外证实了非造血区室的两个不同细胞亚群之间的IL-1依赖性串扰。这些数据建立了真菌感染背景下IL-1和粒细胞生成之间的新联系。总之，我们确定了两种协调口腔粘膜中性粒细胞反应的互补机制，这对于防止真菌生长和传播至关重要，从而保护宿主免受疾病的侵害。条件致病菌白色念珠菌是免疫抑制个体的主要危险因素，口咽念珠菌病（OPC）是细胞免疫减弱患者的常见并发症。细胞因子白细胞介素-17（IL-17）在抗真菌宿主防御中起着关键作用，并被认为通过调节中性粒细胞向口腔粘膜的募集来发挥作用。然而，尽管IL-17在某些情况下可以促进中性粒细胞运输，但我们最近在小鼠模型中表明，在OPC期间并非如此。因此，中性粒细胞对C.白色念珠菌仍有待确定。在这里，我们证明了IL-1受体（IL-1 R）信号转导在通过增强趋化因子分泌和增加骨髓中性粒细胞输出从循环到感染组织的中性粒细胞招募中的重要作用。我们发现，当C.白念珠菌，作用于内皮细胞，诱导产生粒细胞集落刺激因子（G-CSF），这是紧急粒细胞生成的关键触发因素。因此，IL-1 R信号转导将口腔粘膜中对真菌的局部反应转化为全身反应，这对保护免受感染至关重要。
Mucosal infections with Candida albicans belong to the most frequent forms of fungal diseases. Host protection is conferred by cellular immunity; however, the induction of antifungal immunity is not well understood. Using a mouse model of oropharyngeal candidiasis (OPC) we show that interleukin-1 receptor (IL-1R) signaling is critical for fungal control at the onset of infection through its impact on neutrophils at two levels. We demonstrate that both the recruitment of circulating neutrophils to the site of infection and the mobilization of newly generated neutrophils from the bone marrow depended on IL-1R. Consistently, IL-1R-deficient mice displayed impaired chemokine production at the site of infection and defective secretion of granulocyte colony-stimulating factor (G-CSF) in the circulation in response to C. albicans. Strikingly, endothelial cells were identified as the primary cellular source of G-CSF during OPC, which responded to IL-1α that was released from keratinocytes in the infected tissue. The IL-1-dependent crosstalk between two different cellular subsets of the nonhematopoietic compartment was confirmed in vitro using a novel murine tongue-derived keratinocyte cell line and an established endothelial cell line. These data establish a new link between IL-1 and granulopoiesis in the context of fungal infection. Together, we identified two complementary mechanisms coordinating the neutrophil response in the oral mucosa, which is critical for preventing fungal growth and dissemination, and thus protects the host from disease. The opportunistic pathogen Candida albicans is a major risk factor for immunosuppressed individuals, and oropharyngeal candidiasis (OPC) is a frequent complication in patients with weakened cellular immunity. The cytokine interleukin-17 (IL-17) plays a critical role for antifungal host defense and was proposed to act by regulating neutrophil recruitment to the oral mucosa. However, although IL-17 can promote neutrophil trafficking in some situations, we recently showed in a mouse model that this is not the case during OPC. Thus, the mechanism governing the neutrophil response to C. albicans remained to be determined. Here, we demonstrate an essential role of IL-1 receptor (IL-1R) signaling in the recruitment of neutrophils from the circulation to the infected tissue via enhanced secretion of chemokines and increased output of neutrophils from the bone marrow. We found that IL-1α is released from keratinocytes upon invasion of C. albicans and acts on endothelial cells to induce the production of granulocyte colony-stimulating factor (G-CSF), a key trigger of emergency granulopoiesis. Thereby, IL-1R signaling translates the local response to the fungus in the oral mucosa into a systemic response that critically contributes to protection from infection.
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影响因子：
9.2
作者：
Feldmeyer, Laurence;Keller, Martin;Beer, Hans-Dietmar
通讯作者：
Beer, Hans-Dietmar
影响因子：
6.4
作者：
Bruno VM;Shetty AC;Yano J;Fidel PL Jr;Noverr MC;Peters BM
通讯作者：
Peters BM
影响因子：
6.7
作者：
Leal SM Jr;Cowden S;Hsia YC;Ghannoum MA;Momany M;Pearlman E
通讯作者：
Pearlman E
影响因子：
20.3
作者：
Eyles, Jo L.;Hickey, Michael J.;Wicks, Ian P.
通讯作者：
Wicks, Ian P.
DOI：
10.4049/jimmunol.0901323
发表时间：
2009-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Joly S;Ma N;Sadler JJ;Soll DR;Cassel SL;Sutterwala FS
通讯作者：
Sutterwala FS