Helminth Infections Coincident with Active Pulmonary Tuberculosis Inhibit Mono- and Multifunctional CD4+ and CD8+ T Cell Responses in a Process Dependent on IL-10
Helminth Infections Coincident with Active Pulmonary Tuberculosis Inhibit Mono- and Multifunctional CD4+ and CD8+ T Cell Responses in a Process Dependent on IL-10
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DOI：
10.1371/journal.ppat.1004375
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发表时间：
2014-09-01
期刊：
影响因子：
6.7
通讯作者：
Babu, Subash
中科院分区：
文献类型：
--
作者：
George, Parakkal Jovvian;Anuradha, Rajamanickam;Babu, Subash
组织侵入性蠕虫感染和结核病（TB）在世界许多地区共同流行，并可引发可能相互对抗的免疫反应。我们以前已经表明，蠕虫感染调节Th 1和Th 17对潜伏性结核分枝杆菌抗原的反应。为了确定蠕虫感染是否调节活动性肺结核的抗原特异性和非特异性免疫应答，我们检测了伴有或不伴有两种不同蠕虫感染（班氏吴策线虫和粪类圆线虫感染）的肺结核患者的CD 4（+）和CD 8（+）T细胞应答以及全身（血浆）细胞因子水平。通过分析Th 1和Th 17 CD 4（+）和CD 8（+）T细胞及其组分亚群（包括多功能细胞）的频率，我们报告了当同时发生丝虫或类圆线虫感染时，单功能和多功能CD 4（+）Th 1和（在较小程度上）Th 17细胞的分枝杆菌特异性频率显著降低。CD 4（+）和CD 8（+）T细胞细胞因子反应的损伤是抗原特异性的，因为多克隆活化T细胞频率是等同的，与蠕虫感染状态无关。这种T细胞应答的减少也反映在Th 1（IFN-γ、TNF-α和IL-2）-和Th 17（IL-17 A和IL-17 F）-相关细胞因子的循环水平降低中。最后，我们证明，至少对于丝虫合并感染，这种多功能CD 4（+）T细胞应答频率的降低部分依赖于IL-10，因为IL-10阻断显著增加了CD 4（+）Th 1细胞的频率。因此，在活动性肺TB中，共存蠕虫感染与IL-10介导的（对于丝虫感染）抗原特异性CD 4（+）T细胞应答的显著抑制以及保护性全身细胞因子应答相关。
Tissue invasive helminth infections and tuberculosis (TB) are co-endemic in many parts of the world and can trigger immune responses that might antagonize each other. We have previously shown that helminth infections modulate the Th1 and Th17 responses to mycobacterial-antigens in latent TB. To determine whether helminth infections modulate antigen-specific and non-specific immune responses in active pulmonary TB, we examined CD4(+) and CD8(+) T cell responses as well as the systemic (plasma) cytokine levels in individuals with pulmonary TB with or without two distinct helminth infections-Wuchereria bancrofti and Strongyloides stercoralis infection. By analyzing the frequencies of Th1 and Th17 CD4(+) and CD8(+) T cells and their component subsets (including multifunctional cells), we report a significant diminution in the mycobacterial-specific frequencies of mono-and multi-functional CD4(+) Th1 and (to a lesser extent) Th17 cells when concomitant filarial or Strongyloides infection occurs. The impairment in CD4(+) and CD8(+) T cell cytokine responses was antigen-specific as polyclonal activated T cell frequencies were equivalent irrespective of helminth infection status. This diminution in T cell responses was also reflected in diminished circulating levels of Th1 (IFN-gamma, TNF-alpha and IL-2)-and Th17 (IL-17A and IL-17F)-associated cytokines. Finally, we demonstrate that for the filarial co-infections at least, this diminished frequency of multifunctional CD4(+) T cell responses was partially dependent on IL-10 as IL-10 blockade significantly increased the frequencies of CD4(+) Th1 cells. Thus, co-existent helminth infection is associated with an IL-10 mediated (for filarial infection) profound inhibition of antigen-specific CD4(+) T cell responses as well as protective systemic cytokine responses in active pulmonary TB.