Macrophages represent the first line of defense against invading Mycobacterium tuberculosis (Mtb). In order to enhance intracellular survival, Mtb targets various components of the host signaling pathways to limit macrophage functions. The outcome of Mtb infection depends on various factors derived from both host and pathogen. A detailed understanding of such factors operating during interaction of the pathogen with the host is a prerequisite for designing new approaches for combating mycobacterial infections. This work analyzed the role of host phospholipase C‐γ1 (PLC‐γ1) in regulating mycobacterial uptake and killing by J774A.1 murine macrophages. Small interfering RNA mediated knockdown of PLC‐γ1 increased internalization and reduced the intracellular survival of both Mtb and Mycobacterium smegmatis (MS) by macrophages. Down‐regulation of the host PLC‐γ1 was observed during the course of mycobacterial infection within these macrophages. Finally, Mtb infection also suppressed the expression of pro‐inflammatory cytokine tumor necrosis factor‐α and chemokine (C‐C motif) ligand 5 (RANTES) which was restored by knocking down PLC‐γ1 in J774A.1 cells. These observations suggest a role of host PLC‐γ1 in the uptake and killing of mycobacteria by murine macrophages.

中文翻译：

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宿主磷脂酶C-γ1会损害J774A.1鼠巨噬细胞的吞噬作用并杀死分枝杆菌。

巨噬细胞是抵抗入侵的结核分枝杆菌（Mtb）的第一道防线。为了增强细胞内存活，Mtb靶向宿主信号传导途径的各种成分以限制巨噬细胞功能。Mtb感染的结果取决于源自宿主和病原体的各种因素。对病原体与宿主相互作用过程中起作用的这些因素的详细了解，是设计对抗分枝杆菌感染的新方法的前提。这项工作分析了宿主磷脂酶C‐γ1（PLC‐γ1）在调节J774A.1鼠巨噬细胞对分枝杆菌的摄取和杀伤中的作用。小干扰RNA介导的PLC-γ1敲低会增加内在化并降低Mtb和Mtb的细胞内存活率耻垢分枝杆菌（MS）的巨噬细胞。在这些巨噬细胞内的分枝杆菌感染过程中，观察到宿主PLC-γ1的下调。最后，Mtb感染还抑制了促炎性细胞因子肿瘤坏死因子α和趋化因子（CC主题）配体5（RANTES）的表达，这些基因通过敲除J774A.1细胞中的PLC-γ1得以恢复。这些观察结果表明宿主PLC-γ1在鼠巨噬细胞摄取和杀死分枝杆菌中的作用。