Macrophages have been identified as key players within the tumor microenvironment, with classically (M1) and alternatively (M2) activated macrophages exhibiting anti-tumoral and pro-tumoral functions, respectively. The goal of this study was to determine the response of macrophage populations to infection with oncolytic vesicular stomatitis virus (VSV). THP-1 monocytes were differentiated into various macrophage subsets and infected with wild-type (rwt virus) or matrix (M) protein mutant (rM51R-M virus) strains of VSV. Monocytes and M2 macrophages were susceptible to infection and killing by both rwt and rM51R-M viruses. rM51R-M virus also increased expression of the M1 markers p-STAT1, CD80, and TNF-α in pro-tumoral M2 macrophages, suggesting reprogramming towards an M1-like pro-inflammatory state. Meanwhile, rwt virus was more effective than rM51R-M virus at replicating in M2 macrophages and at inhibiting the development of invasive podosome structures. This was all in contrast to anti-tumoral M1 macrophages, which remained resistant to VSV-induced cytopathic effects. These results indicate that macrophage populations are differentially susceptible to VSV and that rwt and rM51R-M viruses may modulate the tumor-promoting phenotype of M2 macrophages by distinct mechanisms.

中文翻译：

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溶瘤性水疱性口炎病毒选择性靶向 M2 巨噬细胞。

巨噬细胞已被确定为肿瘤微环境中的关键参与者，经典 (M1) 和替代 (M2) 激活的巨噬细胞分别表现出抗肿瘤和促肿瘤功能。本研究的目的是确定巨噬细胞群对溶瘤性水泡性口炎病毒 (VSV) 感染的反应。THP-1 单核细胞分化为各种巨噬细胞亚群，并感染 VSV 的野生型（rwt 病毒）或基质（M）蛋白突变体（rM51R-M 病毒）株。单核细胞和 M2 巨噬细胞容易受到 rwt 和 rM51R-M 病毒的感染和杀死。rM51R-M 病毒还增加了促肿瘤 M2 巨噬细胞中 M1 标志物 p-STAT1、CD80 和 TNF-α 的表达，表明重编程为 M1 样促炎状态。同时，rwt 病毒在 M2 巨噬细胞中复制和抑制侵入性足体结构的发展方面比 rM51R-M 病毒更有效。这与抗肿瘤 M1 巨噬细胞形成对比，后者仍然对 VSV 诱导的细胞病变效应具有抗性。这些结果表明巨噬细胞群体对 VSV 的敏感性不同，并且 rwt 和 rM51R-M 病毒可能通过不同的机制调节 M2 巨噬细胞的促肿瘤表型。