Musculoskeletal Research Group, Institute for Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
J Allergy Clin Immunol. 2010 Nov;126(5):1006-15, 1015.e1-4. doi: 10.1016/j.jaci.2010.08.027. Epub 2010 Oct 8.
Accumulating evidence implicates T(H)17 cytokines in protection against Candida species infections, but the clinical relevance is not clear. Chronic mucocutaneous candidiasis (CMC) is a heterogeneous syndrome with the unifying feature of selective susceptibility to chronic candidiasis. Different subgroups with distinct clinical features are recognized, including autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), CMC with hypothyroidism, and isolated CMC. Understanding immune defects in patients with CMC will define cellular and molecular mechanisms crucial for protection against Candida species in human subjects.
We sought to determine whether impaired T(H)17 responses underlie susceptibility to Candida species infections and whether the same defect is present in different CMC subgroups.
We assessed T(H)17 responses of PBMCs to Candida and non-Candida species stimuli by measuring IL-17, IL-22, IL-21, IL-6, IL-23, and IFN-γ cytokine production using cytokine arrays and intracellular cytokine-producing cell numbers and proliferation with flow cytometry. PBMCs from healthy subjects and unaffected family members served as controls.
In patients with CMC with hypothyroidism, T(H)17 cells demonstrated decreased proliferation and IL-17 production in response to Candida species. In contrast, in patients with APECED, T(H)17 cell proliferation and IL-17 production were normal unless exposed to APECED plasma, which inhibited both functions in both APECED and normal PBMCs. Candida species-stimulated IL-22 production was impaired in all patients with CMC, whereas IL-6 and IL-23 responses were unaltered.
An impaired T(H)17 response to Candida species, although mediated by different mechanisms, was present in all CMC subgroups studied and might be a common factor predisposing to chronic candidiasis.
越来越多的证据表明辅助性 T 细胞 17（T(H)17）细胞因子在对抗念珠菌属感染中发挥作用，但临床相关性尚不清楚。慢性黏膜皮肤念珠菌病（CMC）是一种异质性综合征，其特征是对慢性念珠菌病的选择性易感性。目前已识别出具有不同临床特征的不同亚组，包括自身免疫性多内分泌腺病-念珠菌病-外胚层营养不良（APECED）、伴有甲状腺功能减退的 CMC 和孤立性 CMC。了解 CMC 患者的免疫缺陷将确定对人类宿主中念珠菌属的保护具有关键作用的细胞和分子机制。
我们旨在确定 T(H)17 反应受损是否是导致对念珠菌属感染易感性的原因，以及相同的缺陷是否存在于不同的 CMC 亚组中。
我们通过测量细胞因子阵列中的细胞因子产生，以及通过流式细胞术测量细胞内细胞因子产生细胞的数量和增殖，评估了 PBMC 对念珠菌和非念珠菌属物种刺激物的 T(H)17 反应。使用健康受试者和未受影响的家庭成员的 PBMC 作为对照。
在伴有甲状腺功能减退的 CMC 患者中，T(H)17 细胞的增殖和对念珠菌属的 IL-17 产生减少。相比之下，在 APECED 患者中，除非暴露于 APECED 血浆，否则 T(H)17 细胞的增殖和 IL-17 产生正常，而 APECED 血浆抑制了 APECED 和正常 PBMC 中的这两种功能。所有 CMC 患者的念珠菌属刺激的 IL-22 产生受损，而 IL-6 和 IL-23 反应无变化。
尽管机制不同，但在所有研究的 CMC 亚组中都存在对念珠菌属的受损 T(H)17 反应，这可能是导致慢性念珠菌病的一个共同因素。
