Obesity uncovers presence of inflammatory lung macrophage subsets with adipose tissue transcriptomic signature in influenza virus infection.

Abstract

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.