Interplay of interferon-gamma and macrophage polarization during Talaromyces marneffei infection
Interplay of interferon-gamma and macrophage polarization during Talaromyces marneffei infection
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DOI：
10.1016/j.micpath.2019.103594
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发表时间：
2019-09-01
影响因子：
3.8
通讯作者：
Calderone, Richard
中科院分区：
文献类型：
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作者：
Lu, Sha;Li, Dongmei;Calderone, Richard
在临床环境中，马尔尼菲塔芳香菌是一种破坏性越来越大的二态真菌病原体，可引起致命的塔芳香菌病。众所周知，巨噬细胞的激活对于宿主防御T. marneffei非常重要，并且这些巨噬细胞以两种方式激活（极化），称为M1和M2。我们研究了这些极化的可塑性，以了解巨噬细胞的交叉转化是否可能，甚至在它们被编程后。我们使用小鼠巨噬细胞细胞系进行了体外实验，以研究T. marneffei激活这些极化的能力。用LPS刺激前极化（M0）巨噬细胞亚群作为对照，并评估M1标记物（iNOS和CD86）和M2标记物（Arg-1和CD206）在M1、M2和M0（未刺激）群体之间可能的交叉转化。我们发现，无论是分生孢子还是酵母形式的马尼菲T. marneffei都能在M2细胞中抑制Arg-1，而M1亚型标记分子iNOS没有变化。然而，额外的ifn - γ刺激导致三种巨噬细胞组完全表现出lps诱导的M2抑制，并从M0和M2向M1转移。我们得出结论，巨噬细胞的转化是维持宿主体内对抗这种生物的足够iNOS产生所必需的。细胞因子环境是调控巨噬细胞亚型间可塑性变化的关键因素。此外，ifn - γ是一种重要的宿主防御因子，可抵抗致病性马氏弓形虫，具有促进M1极化表型的显著治疗潜力。
Talaromyces marneffei is an increasingly destructive dimorphic fungal pathogen in clinical settings that can cause lethal Talaromycosis. The activation of macrophages is known to be important for host defenses against T. marneffei, and these macrophages are known to be activated in two ways (polarization), known as M1 and M2. We investigated the plasticity of these polarizations, in order to understand if cross-conversion of macrophages may be possible even after they have been programmed. We conducted in vitro experiments using a murine macrophage cell line to investigate the ability of T. marneffei to activate these polarizations. The pre-polarized (M0) macrophage subsets were challenged with LPS as a control, and the sets of M1 markers (iNOS and CD86) and M2 markers (Arg-1 and CD206) were assessed for a possible cross-conversion among M1, M2 and M0 (unstimulated) populations. We found that either conidia or yeast forms of T. marneffei initiate the repression of Arg-1 in M2 cells with no change in the M1 subtype marker molecule iNOS. However, an additional IFN-gamma stimulus caused the three macrophage groups to fully exhibit an LPS-induced M2 suppression and a shift to M1 from M0 and M2. We conclude that the conversion of macrophages is required for maintenance of sufficient iNOS production against this organism in the host. The cytokine environment is the key factor that manipulates the plasticity changes among macrophage subtypes. Furthermore, IFN-gamma is a crucial host defense factor against pathogenic T. marneffei that has significant therapeutic potential to promote an M1 polarization phenotype.