The Cytokine and Chemokine Response to Influenza Virus Infection in Neonatal Mice

Abstract

Influenza virus is an important cause of mortality and morbidity in children. However, little data exists on the neonatal immune response to influenza virus. We studied intranasal influenza virus infection in adult and 2 day‐old mice, and found that the LD10 for pups is 10 fold lower than for adults. We also observed an interstitial distribution of T cells in the lungs of influenza virus infected pups. By 14 days post infection, the numbers of CD4 and CD8 T cells in the lung interstitia were comparable between pups and adults. However, in pups, T cells were absent from the airways. We therefore determined the mRNA levels of chemokines in lungs from infected pups and adults. Interestingly, in pups, CCL5 (RANTES) expression was elevated, while CXCL9 (MIG) expression was reduced by over 10 fold compared to adult mice. We previously found that TGFβ is constitutively expressed in neonatal lungs, so we examined TGFβ in the context of influenza virus infection. Total TGFβ levels dropped after infection in adults, but remained elevated in pup lungs throughout infection. This corresponded to reduced IFNγ. Consistent with this cytokine profile, a lower level of pup T cells expressed markers of activation. Together, these data suggest that the immune response to influenza infection in neonates is hindered by inappropriate expression of cytokines and chemokines.Supported by an AHA predoctoral fellowship.