Parasite Antigen-Specific Regulation of Th1, Th2, and Th17 Responses in Strongyloides stercoralis Infection.
Parasite Antigen-Specific Regulation of Th1, Th2, and Th17 Responses in Strongyloides stercoralis Infection.
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DOI：
10.4049/jimmunol.1500745
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发表时间：
2015-09-01
期刊：
影响因子：
--
通讯作者：
Babu S
中科院分区：
文献类型：
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作者：
Anuradha R;Munisankar S;Dolla C;Kumaran P;Nutman TB;Babu S
已知慢性蠕虫感染与抗原特异性CD 4 + T应答的调节有关。然而，CD 4 + T细胞反应在人类感染粪类圆线虫（Ss）中的作用尚未明确。为了研究表达Th 1、Th 2和Th 17细胞因子的CD 4 + T细胞在类圆线虫病中的作用，我们比较了感染个体（INF）中这些亚群的频率（Fo）和未感染（UN）个体中的频率（Fo）。与UN相比，INF个体表现出单功能和双功能Th 1细胞的自发性和抗原特异性Fo的显著降低。类似地，与UN相比，INF个体在抗原刺激后也表现出单功能和双功能Th 17细胞的Fo显著降低。相反，与UN个体相比，INF中单功能和双功能Th 2细胞的自发和抗原诱导的Fo均显著增加。这种差异性T细胞应答主要是抗原特异性的，因为它在对照抗原或有丝分裂原刺激后被消除。Th 1、Th 2和Th 17细胞的调节主要依赖于IL-10，而Th 2细胞的调节也依赖于TGFβ，而不是Th 1或Th 17细胞。此外，Ss感染治疗显著增加INF个体中Th 1和Th 17细胞的抗原特异性Fo，并降低Th 2细胞的Fo。因此，Ss感染的特征在于单功能和双功能Th 1、Th 2和Th 17细胞的寄生虫抗原依赖性调节，这种调节也可通过抗蠕虫治疗逆转。
Chronic helminth infections are known to be associated with modulation of antigen - specific CD4+ T responses. However, the role of CD4+ T cell responses in human infection with Strongyloides stercoralis (Ss) is not well-defined. To examine the role of CD4+ T cells expressing Th1, Th2 and Th17 cytokines in strongyloidiasis, we compared the frequency of these subsets in infected individuals (INF) to frequencies (Fo) in Ss-uninfected (UN) individuals. INF individuals exhibited a significant decrease in the spontaneous and antigen specific Fo of both mono - and dual functional Th1 cells compared to UN. Similarly, INF individuals also exhibited significantly decreased Fo of mono - and dual - functional Th17 cells upon antigen - stimulation compared to UN. In contrast, both the spontaneous and antigen - induced Fo of mono- and dual - functional Th2 cells was significantly increased in INF compared to UN individuals. This differential T cell response was predominantly antigen - specific since it was abrogated upon control antigen or mitogen stimulation. The regulation of Th1, Th2 and Th17 cells was pre-dominantly dependent on IL-10, while the regulation of Th2 but not Th1 or Th17 cells was also dependent on TGFβ. In addition, treatment of Ss infection significantly increased the antigen - specific Fo of Th1 and Th17 cells and decreased the Fo of Th2 cells in INF individuals. Thus, Ss infection is characterized by a parasite - antigen dependent regulation of mono- and dual - functional Th1, Th2 and Th17 cells, a regulation also reversible by anti-helminthic treatment.