Obesity is a risk factor for increased lung damage and disease severity during influenza virus infection. White adipose tissue (WAT) inflammation is a key driver of disease pathogenesis in obesity. Whether and how obesity modifies lung and WAT immune cell character and function in obesity to amplify influenza disease severity remains unknown. We show that obesity establishes a proinflammatory transcriptome in lung immune cells that is further augmented upon influenza virus infection. Unexpectedly, we also show that influenza virus infection induces expression of inflammatory genes in visceral WAT and modifies WAT immune cell milieu in obesity. Notably, a decrease in WAT macrophage (ATM) populations inversely correlates to increase in infiltrating lung macrophage numbers in obese influenza virus-infected mice. Comparison of both lung and WAT immune cell transcriptional landscapes uncovers a presence of a macrophage subset in the lungs whose transcriptomic signatures matched those of an inflammatory ATM subset preferentially found in obese mice. Adoptive transfer of ATMs from obese mice into lean influenza-virus infected mice promotes host immune cell infiltration to the lungs. Together, our novel findings provide evidence of immune cell transcriptome and character changes in the lungs and WAT of influenza virus infected obese, but not lean, mice and suggest that visceral ATMs may contribute to the overall inflammatory milieu in this setting.

中文翻译：

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肥胖发现流感病毒感染中存在具有脂肪组织转录组学特征的炎性肺巨噬细胞亚群


肥胖是流感病毒感染期间肺损伤和疾病严重程度增加的危险因素。白色脂肪组织 （WAT） 炎症是肥胖疾病发病机制的关键驱动因素。肥胖是否以及如何改变肥胖中的肺和 WAT 免疫细胞特征和功能以放大流感疾病的严重程度仍然未知。我们表明，肥胖在肺免疫细胞中建立了促炎转录组，该转录组在流感病毒感染后进一步增强。出乎意料的是，我们还表明流感病毒感染诱导内脏 WAT 中炎症基因的表达，并改变肥胖中的 WAT 免疫细胞环境。值得注意的是，在肥胖流感病毒感染的小鼠中，WAT 巨噬细胞 （ATM） 种群的减少与浸润性肺巨噬细胞数量的增加呈负相关。肺和 WAT 免疫细胞转录景观的比较揭示了肺中存在巨噬细胞亚群，其转录组特征与优先在肥胖小鼠中发现的炎性 ATM 亚群相匹配。ATM 从肥胖小鼠过继转移到瘦流感病毒感染小鼠中，促进宿主免疫细胞浸润到肺部。总之，我们的新发现提供了流感病毒感染的肥胖但不瘦小鼠的肺部和 WAT 免疫细胞转录组和特征变化的证据，并表明在这种情况下，内脏 ATM 可能有助于整体炎症环境。