PM2.5, a major component of air pollutants, has caused severe health problems. It has been reported that PM2.5 index is closely associated with severity of influenza A virus (IAV) infection. However, the underlying mechanisms have not been addressed. NLRP3 inflammasome and type I interferon signaling regulate host defense against influenza infection. The present study investigated the potential effects of air pollutants on host defense against influenza infection in vitro and in vivo. In this study, different concentrations of PM2.5 were pre-exposed to macrophages and mice before IAV infection to assess the negative effects of air pollutants in virus infection. We found that exposure to PM2.5 deteriorated influenza virus infection via compromising innate immune responses manifested by a decrease IL-1β and IFN-β production in vitro. Meanwhile, mice exposed with PM2.5 were susceptible to PR8 virus infection due to down-regulation of IL-1β and IFN-β. Mechanistically, PM 2.5 exposure suppressed the NLRP3 inflammasome activation and the AHR-TIPARP signaling pathway, by which compromised the anti-influenza immunity. Thus, our study revealed that PM2.5 could alter macrophage inflammatory responses by suppressing LPS-induced activation of NLRP3 inflammasome and expression of IFN-β during influenza infection. These findings provided us new insights in understanding that PM2.5 combining with influenza infection could enhance the severity of pneumonia.

中文翻译：

---

PM2.5通过抑制NLRP3炎性小体的激活和干扰素-β的表达来削弱流感病毒感染中的抗病毒免疫性。

PM2.5是空气污染物的主要成分，已引起严重的健康问题。据报道，PM2.5指数与甲型流感病毒（IAV）感染的严重程度密切相关。但是，底层机制尚未解决。NLRP3炎性小体和I型干扰素信号传导调节宿主防御流感感染的能力。本研究调查了空气污染物在宿主体内和体内对流感感染宿主防御的潜在影响。在这项研究中，在IAV感染之前，巨噬细胞和小鼠预先暴露了不同浓度的PM2.5，以评估空气污染物对病毒感染的负面影响。我们发现暴露于PM2.5会通过损害先天免疫应答而恶化流感病毒感染，这种先天免疫应答在体外可降低IL-1β和IFN-β的产生。与此同时，暴露于PM2.5的小鼠由于IL-1β和IFN-β的下调而容易感染PR8病毒。从机理上讲，PM 2.5暴露抑制了NLRP3炎性体的激活和AHR-TIPARP信号通路，从而削弱了抗流感免疫力。因此，我们的研究表明，PM2.5可以通过抑制LPS诱导的流感病毒感染期间NLRP3炎性小体的激活和IFN-β的表达来改变巨噬细胞的炎症反应。这些发现为我们提供了新的见解，以了解PM2.5结合流感感染可增强肺炎的严重性。从而削弱了抗流感免疫力。因此，我们的研究表明，PM2.5可以通过抑制LPS诱导的流感病毒感染期间NLRP3炎性小体的激活和IFN-β的表达来改变巨噬细胞的炎症反应。这些发现为我们提供了新的见解，以了解PM2.5结合流感感染可增强肺炎的严重性。从而削弱了抗流感免疫力。因此，我们的研究表明，PM2.5可以通过抑制LPS诱导的流感病毒感染期间NLRP3炎性小体的激活和IFN-β的表达来改变巨噬细胞的炎症反应。这些发现为我们提供了新的见解，以了解PM2.5结合流感感染可增强肺炎的严重性。