NFAT1 Regulates Ly6C Monocyte Recruitment to the CNS and Plays an Essential Role in Resistance to Infection.

Monocytes play key roles in the maintenance of homeostasis and in the control of the infection. Monocytes are recruited from the bone marrow to inflammatory sites and are essential for antimicrobial activity to limit tissue damage and promote adaptive T cell responses. Here, we investigated the role of Nuclear Factor of Activated T cells 1 (NFAT1) in the regulation of Ly6C inflammatory monocyte recruitment to the CNS upon infection. We show that NFAT-1-deficient monocytes are unable to migrate to the CNS of -infected mice. Moreover, NFAT1 mice are highly susceptible to chronic infection due to a failure to control parasite replication in the CNS. The inhibition of Ly6C inflammatory monocyte recruitment to the CNS severely blocked CXCL10 production and consequently the migration of IFN-γ-producing CD4 T cells. Moreover, the transfer of Ly6C monocytes to infected NFAT1 mice favored CD4 T cell migration to the CNS and resulted in the inhibition of parasite replication and host defense. Together, these results demonstrated for the first time the contribution of NFAT1 to the regulation of Ly6C monocyte recruitment to the CNS and to resistance during chronic infection.