Influenza Infection Promotes Lung Accrual of Macrophages with an Obese Adipose Tissue Transcriptomic Signature

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. While lung tissue immune cell pathogenic mechanisms are dogmatically studied in influenza virus infection, how obesity modifies lung and WAT immune cell character and contribution to amplify disease severity remains unknown. We show that obesity results in lung immune cells having a more inflammatory transcriptome in response to influenza infection than in the lean state. Further, in both lean and obese mice, influenza virus infection induces expression of inflammatory genes in visceral WAT and dominantly modifies the WAT immune cell milieu in obesity. Notably, obese influenza virus-infected mice exhibit a decrease in white adipose tissue macrophage (ATM) populations that inversely correlates with the increase in infiltrating lung macrophage numbers. Overall design: Comparison of both lung and WAT immune cell transcriptional landscapes uncovered a presence of a macrophage subset in the lungs whose transcriptomic signatures matched those of an inflammatory ATM subset seen in obese mice. Notably, adoptive transfer of ATMs from obese mice into lean influenza-virus infected mice resulted in increased host immune cell lung infiltration. Together, our novel findings provide transcriptomic evidence of obesity-driven changes in immune cell character in the lungs and WAT and identify a previously unrecognized contribution of visceral ATMs to exacerbated influenza disease severity in obesity.