Aging promotes neutrophil-induced mortality by augmenting IL-17 production during viral infection.
Morbidity and mortality associated with viral infections increase with age, although the underlying mechanisms are unclear. Here, we investigated whether aging alters inflammatory responses during systemic viral infection and thereby contributes to virus-induced death. We found that infection of aged mice with systemic herpes viruses led to rapid increases in serum IL-17, neutrophil activation, and mortality due to hepatocyte necrosis. In contrast, all young mice survived infection, displaying weaker IL-17 induction and neutrophil activation. Natural killer T (NKT) cells isolated from the livers of aged mice produced more IL-17 than did young cells, and adoptively transferred aged NKT cells induced liver injury in young mice impaired in viral control. Importantly, IL-17 neutralization or neutrophil depletion during viral infection reduced liver damage and prevented death of aged mice. These results demonstrate that, during systemic viral infection, aging alters the host-pathogen interaction to overproduce IL-17, contributing to liver injury and death.
Stout-Delgado
Heather W
HW
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8018, USA.
Du
Wei
W
Shirali
Anushree C
AC
Booth
Carmen J
CJ
Goldstein
Daniel R
DR
D000375:Aging / Q000276:immunology*; D000818:Animals; D022781:Hepatocytes / Q000473:pathology; D006561:Herpes Simplex / Q000276:immunology* / Q000401:mortality* / Q000503:physiopathology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D007249:Inflammation; D020381:Interleukin-17 / Q000378:metabolism*; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D008213:Lymphocyte Activation; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000821:virology; D009336:Necrosis; D018375:Neutrophil Activation / Q000276:immunology*; D015854:Up-Regulation
D020381:Interleukin-17