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Publication : NFAT1 Regulates Ly6C<sup>hi</sup> Monocyte Recruitment to the CNS and Plays an Essential Role in Resistance to <i>Toxoplasma gondii</i> Infection.

First Author  Benevides L Year  2019
Journal  Front Immunol Volume  10
Pages  2105 PubMed ID  31555297
Mgi Jnum  J:282113 Mgi Id  MGI:6381127
Doi  10.3389/fimmu.2019.02105 Citation  Benevides L, et al. (2019) NFAT1 Regulates Ly6C(hi) Monocyte Recruitment to the CNS and Plays an Essential Role in Resistance to Toxoplasma gondii Infection. Front Immunol 10:2105
abstractText  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(hi) inflammatory monocyte recruitment to the CNS upon T. gondii infection. We show that NFAT-1-deficient monocytes are unable to migrate to the CNS of T. gondii-infected mice. Moreover, NFAT1(-/-) mice are highly susceptible to chronic T. gondii infection due to a failure to control parasite replication in the CNS. The inhibition of Ly6C(hi) inflammatory monocyte recruitment to the CNS severely blocked CXCL10 production and consequently the migration of IFN-gamma-producing CD4(+) T cells. Moreover, the transfer of Ly6C(hi) 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(hi) monocyte recruitment to the CNS and to resistance during chronic T. gondii infection.
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