PARP1-NFATc1-PD1 pathway of maturation and stability of CD8T cells is beneficial against chronic infection.

Poly(ADP-ribose) polymerase 1 (PARP1) inhibition improved the ventricular function in Chagas disease (CD). Here, we uncovered that depletion enhances cardiac health by regulating CD8T cell response against () infection. For this, and wild-type (WT) mice were challenged with and euthanized at acute and chronic phases of parasite replication and CD development, respectively. mice controlled the chronic parasite persistence and associated inflammatory pathology more effectively than WT mice. enhanced the maturation and stability of metabolically reprogrammed CD8 effector and memory T cells with increased cytotoxic effects against the parasite. Mechanistically, PARP1 depletion enhanced the NFATc1 translocation to Pdcd1 promoter in CD8T cells, altered the PD1:PDL1 stoichiometric ratio between CD8T and antigen-presenting cells, and promoted CD8T cell longevity and function during chronic infection. We conclude that molecular and chemical inhibitors of PARP1 would offer a potential therapy to arrest CD pathogenesis.