Autophagy in dendritic cells modulates CD4+ T cell response during RSV infection (106.9)

Abstract

Abstract Severe respiratory syncytial virus (RSV) infections cause significant morbidity among susceptible individuals, especially infants. During viral infection, dendritic cells (DC) prime appropriate adaptive immune responses through antigen presentation, cytokine production and costimulation of T cells. Previous studies suggest that macroautophagy, an intracellular process delivering cytoplasmic constituents to endosomes for degradation, functions in intracellular pathogen surveillance and antigen delivery for presentation by DC. RSV infection of bone marrow-derived dendritic cells (BMDC) stimulates autophagosome formation, while siRNA knockdown of LC3 prior to RSV infection reduces innate cytokine production. Pulmonary DCs from RSV-infected LC3b-deficient mice show dysregulated maturation through altered MHC class II and costimulatory molecule expression. BMDC cultured from LC3b-deficient mice skew primary and secondary T cell responses toward Th17, while decreasing expression of IFNγ and Th2 cytokines. These results suggest that virally-induced autophagy in DC modulates the host response to RSV infection through altered activation of CD4+ T cells.