The protective role of γδ T cells in neonatal influenza

Abstract

Abstract Influenza infection is a continuing worldwide health threat, especially in infants and the elderly. Neonates are highly susceptible to influenza infection, which is often causing hospitalization. γδ T cells are the first T cells to develop during embryogenesis and are a significant component of the neonatal immune system. In the neonatal period, conventional αβ T cell responses are functionally less prominent. Hence, γδ T cells are poised to play a critical role in neonatal infections, however, the specific role of γδ T cells in neonatal influenza infection remains to be elucidated. Using a neonatal mouse model of intranasal influenza infection, we observed the activation and proliferation of γδ T cells within two days after infection. By utilizing Nur77-GFP reporter mice, we demonstrated that the activation of γδ T cells was via the TCR and its downstream signaling. IL-17-producing γδ T cells, rather than IFN-γ-producing cells, dominated in the response. A comparison between wild-type and TCRδ-deficient neonates identified a protective function of γδ T cells in neonates, as reduced weight loss and an increased survival rate were observed in the wild-type compared to knockout animals. In infected lungs, wild-type neonates also had more robust IFN-β production and increased inflammatory cytokine production, especially among the Type 2 cytokines, than the TCRδ-deficient animals. Consistently, more eosinophils infiltrated into the lungs of wild-type neonates. Our findings demonstrate a vital role for γδ T cells in mediating protection during neonatal influenza virus infection via a mechanism which appears to include promotion of a Type 2 immune environment that may provide a new therapeutic target for pediatric influenza treatment.