%0 Journal Article
%T Respiratory Virus-Induced PARP1 Alters DC Metabolism and Antiviral Immunity Inducing Pulmonary Immunopathology.
%A Mire MM
%A Elesela S
%A Morris S
%A Corfas G
%A Rasky A
%A Lukacs NW
%J Viruses
%V 16
%N 6
%D 2024 Jun 4
%M 38932202
%F 5.818
%R 10.3390/v16060910
%X Previous studies from our laboratory and others have established the dendritic cell (DC) as a key target of RSV that drives infection-induced pathology. Analysis of RSV-induced transcriptomic changes in RSV-infected DC revealed metabolic gene signatures suggestive of altered cellular metabolism. Reverse phase protein array (RPPA) data showed significantly increased PARP1 phosphorylation in RSV-infected DC. Real-time cell metabolic analysis demonstrated increased glycolysis in PARP1-/- DC after RSV infection, confirming a role for PARP1 in regulating DC metabolism. Our data show that enzymatic inhibition or genomic ablation of PARP1 resulted in increased ifnb1, il12, and il27 in RSV-infected DC which, together, promote a more appropriate anti-viral environment. PARP1-/- mice and PARP1-inhibitor-treated mice were protected against RSV-induced immunopathology including airway inflammation, Th2 cytokine production, and mucus hypersecretion. However, delayed treatment with PARP1 inhibitor in RSV-infected mice provided only partial protection, suggesting that PARP1 is most important during the earlier innate immune stage of RSV infection.