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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Human phagosome processing of Mycobacterium tuberculosis antigens is modulated by interferon-γ and interleukin-10
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Human phagosome processing of Mycobacterium tuberculosis antigens is modulated by interferon-γ and interleukin-10

机译：干扰素-γ和白介素-10调节结核分枝杆菌抗原的人类吞噬过程

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摘要

Intracellular pathogens, such as Mycobacterium tuberculosis, reside in the phagosomes of macrophages where antigenic processing is initiated. Mycobacterial antigen-MHC class II complexes are formed within the phagosome and are then trafficked to the cell surface. Interferon-γ (IFN-γ) and interleukin-10 (IL-10) influence the outcome of M. tuberculosis infection; however, the role of these cytokines with regard to the formation of M. tuberculosis peptide-MHC-II complexes remains unknown. We analysed the kinetics and subcellular localization of M. tuberculosis peptide-MHC-II complexes in M. tuberculosis-infected human monocyte-derived macrophages (MDMs) using autologous M. tuberculosis-specific CD4+ T cells. The MDMs were pre-treated with either IFN-γ or IL-10 and infected with M. tuberculosis. Cells were mechanically homogenized, separated on Percoll density gradients and manually fractionated. The fractions were incubated with autologous M. tuberculosis -specific CD4+ T cells. Our results demonstrated that in MDMs pre-treated with IFN-γ, M. tuberculosis peptide-MHC-II complexes were detected early mainly in the phagosomal fractions, whereas in the absence of IFN-γ, the complexes were detected in the endosomal fractions. In MDMs pre-treated with IL-10, the M. tuberculosis peptide-MHC-II complexes were retained in the endosomal fractions, and these complexes were not detected in the plasma membrane fractions. The results of immunofluorescence microscopy demonstrated the presence of Ag85B associated with HLA-DR at the cell surface only in the IFN-γ-treated MDMs, suggesting that IFN-γ may accelerate M. tuberculosis antigen processing and presentation at the cell membrane, whereas IL-10 favours the trafficking of Ag85B to vesicles that do not contain LAMP-1. Therefore, IFN-γ and IL-10 play a role in the formation and trafficking of M. tuberculosis peptide-MHC-II complexes.
机译：细胞内病原体，例如结核分枝杆菌，驻留在巨噬细胞的吞噬体中，在该处噬菌体开始了抗原加工。分枝杆菌抗原-MHC II类复合物在吞噬体内形成，然后被运输到细胞表面。干扰素-γ（IFN-γ）和白介素10（IL-10）影响结核分枝杆菌感染的结果;然而，这些细胞因子在结核分枝杆菌肽-MHC-II复合物形成中的作用仍然未知。我们分析了使用自体结核分枝杆菌特异性CD4 + T细胞在结核分枝杆菌感染的人单核细胞衍生的巨噬细胞（MDM）中的结核分枝杆菌肽-MHC-II复合物的动力学和亚细胞定位。 MDM用IFN-γ或IL-10预处理，并感染了结核分枝杆菌。机械均质化细胞，在Percoll密度梯度上分离并手动分级。将级分与自体结核分枝杆菌特异性CD4 + T细胞一起温育。我们的结果表明，在用IFN-γ预处理的MDM中，结核分枝杆菌肽-MHC-II复合物主要在吞噬体部分中被早期检测到，而在没有IFN-γ的情况下，在内体部分中被检测到复合物。在用IL-10预处理的MDM中，结核分枝杆菌肽-MHC-II复合物保留在内体组分中，而这些复合物在质膜组分中未检测到。免疫荧光显微镜检查的结果表明，仅在经过IFN-γ处理的MDM中，在细胞表面存在与HLA-DR相关的Ag85B，这表明IFN-γ可以加速结核分枝杆菌抗原的加工和在细胞膜的呈递，而IL -10有利于将Ag85B转运至不含LAMP-1的囊泡。因此，IFN-γ和IL-10在结核分枝杆菌肽-MHC-II复合物的形成和运输中起作用。

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