A role for dectin-1 in the CNS during chronic Toxoplasma gondii infection (MPF5P.739)

Abstract

Abstract The latent stage of T.gondii infection is characterized by the formation of tissue cysts within the CNS. These tissue cysts are formed by manipulation of the parasitophorous vacuole, and chitin is a structural component of the cyst wall. Our lab has shown that Toxoplasma cysts induce an M2 phenotype in macrophages in a contact-dependent manner. Upon contact, these macrophages actively secrete the mammalian chitinase, AMCase, to break down the cyst wall. We have previously demonstrated that AMCase production by macrophages is essential for control of cyst burden in the brain during T. gondii infection. The molecular interactions involved in macrophage-cyst recognition, and the signaling pathway for AMCase production are as yet unknown. Although chitin recognition has been poorly defined, studies suggest dectin-1 may be a receptor. Here, we present data on a role for dectin-1 during T. gondii infection. Dectin-1 is upregulated in the brain in response to infection and is expressed on arginase-1+, M2 macrophages. Consistent with dectin-1 expression on M2 macrophages, dectin-1 is not required to control parasite burden or induce an inflammatory immune response in vivo. However, dectin-1 deficient mice do exhibit trends towards decreased cyst numbers in the brain and a concomitant increase in AMCase transcripts and AMCase activity ex vivo. Thus, this data suggests that dectin-1 is modulating the immune response and chitinase production during chronic Toxoplasma infection.