Alarcon Pablo C, Ulanowicz Cassidy J, Damen Michelle S M A, Eom John, Sawada Keisuke, Chung Hak, Alahakoon Tara, Oates Jarren R, Wayland Jennifer L, Stankiewicz Traci E, Moreno-Fernandez Maria E, Zacharias William J, Salomonis Nathan, Divanovic Senad
Department of Pediatrics, College of Medicine, University of Cincinnati.
Division of Immunobiology, Cincinnati Children's Hospital Medical Center.
J Infect Dis. 2025 Feb 20;231(2):e317-e327. doi: 10.1093/infdis/jiae535.
Obesity is an independent risk factor for increased disease severity during influenza A virus (IAV) infection. White adipose tissue (WAT) inflammation promotes disease pathogenesis in obesity. Whether obesity modifies lung and WAT immune cells to amplify influenza severity is unknown. We show that obesity establishes a proinflammatory transcriptome in lung immune cells that is augmented during IAV infection and that IAV infection changes WAT immune cell milieu in obesity. Notably, a decrease in WAT macrophages (ATM) inversely correlates with an increase in infiltrating lung macrophages in obese IAV-infected mice. Further analyses of lung immune cell uncovered a macrophage subset that shares a transcriptomic signature with inflammatory ATMs. Importantly, adoptive transfer of ATMs from obese mice into lean IAV infected mice promotes host immune cell infiltration to the lungs. These findings suggest that, in an obese state, ATMs may exacerbate the inflammatory milieu important in pathologic responses to IAV infection.
肥胖是甲型流感病毒（IAV）感染期间疾病严重程度增加的独立危险因素。白色脂肪组织（WAT）炎症促进肥胖状态下的疾病发病机制。肥胖是否会改变肺和WAT免疫细胞以加剧流感严重程度尚不清楚。我们发现，肥胖在肺免疫细胞中建立了一种促炎转录组，在IAV感染期间会增强，并且IAV感染会改变肥胖状态下WAT免疫细胞环境。值得注意的是，肥胖的IAV感染小鼠中，WAT巨噬细胞（ATM）的减少与浸润性肺巨噬细胞的增加呈负相关。对肺免疫细胞的进一步分析发现了一个与炎性ATM具有相同转录组特征的巨噬细胞亚群。重要的是，将肥胖小鼠的ATM过继转移到瘦弱的IAV感染小鼠中会促进宿主免疫细胞浸润到肺部。这些发现表明，在肥胖状态下，ATM可能会加剧对IAV感染的病理反应中重要的炎症环境。
