Interleukin-17-Induced Protein Lipocalin 2 Is Dispensable for Immunity to Oral Candidiasis
Interleukin-17-Induced Protein Lipocalin 2 Is Dispensable for Immunity to Oral Candidiasis
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DOI：
10.1128/iai.01389-13
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发表时间：
2014-03-01
影响因子：
3.1
通讯作者：
Gaffen, Sarah L.
中科院分区：
文献类型：
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作者：
Ferreira, Maria Carolina;Whibley, Natasha;Gaffen, Sarah L.
口咽念珠菌病是由共生微生物白色念珠菌引起的一种机会性真菌感染。对OPC的免疫强烈依赖于CD4(+)T细胞，特别是Th17亚群的细胞。白介素17(IL-17)缺乏会导致慢性皮肤黏膜念珠菌病，但IL-17介导的宿主防御的具体下游机制尚不清楚。Lipocalin 2(Lcn2；24p3；中性粒细胞明胶酶相关Lipocalin[NGAL])是一种抗炎细胞因子，尤其是IL-17产生的抗微生物宿主防御因子。Lcn2在防止利用儿茶酚型铁载体的细菌获取铁方面起着关键作用，而Lipocalin 2(-/-)小鼠对大肠杆菌和肺炎克雷伯氏菌的感染非常敏感。Lcn2在介导真菌免疫中的作用尚不清楚。因此，在这项研究中，我们评估了Lcn2在口腔白念珠菌感染免疫中的作用。Lcn2在口腔感染白念珠菌后强烈上调，在IL-17信号转导有缺陷的小鼠(IL-17RA(-/-)或Act1(-/-)小鼠)中其表达几乎完全被取消。然而，Lcn2(-/-)小鼠对OPC完全耐药，与野生型(WT)小鼠相比。此外，Lcn2缺乏介导了对类固醇免疫抑制诱导的OPC的保护作用。因此，尽管Lcn2在白色念珠菌感染过程中有很强的调节作用，但对粘膜念珠菌病的免疫并不需要Lcn2。
Oropharyngeal candidiasis (OPC; thrush) is an opportunistic fungal infection caused by the commensal microbe Candida albicans. Immunity to OPC is strongly dependent on CD4(+) T cells, particularly those of the Th17 subset. Interleukin-17 (IL-17) deficiency in mice or humans leads to chronic mucocutaneous candidiasis, but the specific downstream mechanisms of IL-17 mediated host defense remain unclear. Lipocalin 2 (Lcn2; 24p3; neutrophil gelatinase-associated lipocalin [NGAL]) is an antimicrobial host defense factor produced in response to inflammatory cytokines, particularly IL-17. Lcn2 plays a key role in preventing iron acquisition by bacteria that use catecholate-type siderophores, and lipocalin 2(-/-) mice are highly susceptible to infection by Escherichia coli and Klebsiella pneumoniae. The role of Lcn2 in mediating immunity to fungi is poorly defined. Accordingly, in this study, we evaluated the role of Lcn2 in immunity to oral infection with C. albicans. Lcn2 is strongly upregulated following oral infection with C. albicans, and its expression is almost entirely abrogated in mice with defective IL-17 signaling (IL-17RA(-/-) or Act1(-/-) mice). However, Lcn2(-/-) mice were completely resistant to OPC, comparably to wild-type (WT) mice. Moreover, Lcn2 deficiency mediated protection from OPC induced by steroid immunosuppression. Therefore, despite its potent regulation during C. albicans infection, Lcn2 is not required for immunity to mucosal candidiasis.