Chemoattractant regulation of Toxoplasma gondii-induced encephalitis (58.4)

Abstract

Abstract Some leukocyte chemoattractants and their receptors have been reported to regulate outcome in T. gondii infection of mice, however, most have not yet been evaluated. We have begun to systematically and comprehensively survey chemoattractant receptors in T. gondii infection, using the natural peroral route of administration of the organism. Chemoattractant receptor mRNA was quantified from brain extracts from C57BL/6 mice infected with 10 cysts of the ME49 strain. Parasitism peaked in the brain on the 25th day post infection, and infection was uniformly fatal by day 100. The organism induced expression of the pro-inflammatory chemoattractant receptors C5L2, Ccr1 and Ccr5; the decoy receptors, Ccrl2 and CMKLR1; and the constitutively expressed receptor ligand Cx3cl1. Mice lacking the Cx3cl1 receptor Cx3cr1 had accelerated mortality, whereas mortality was delayed in mice lacking Fpr1, a classical chemoattractant receptor. Unexpectedly, animals infected with T. gondii also had a substantial increase of Ccr7 mRNA during the entire chronic phase, and Ccr7-/- mice exhibited dramatically increased mortality, in comparison with WT mice. The poster will focus on Ccr7, delineating the microbiologic and immunologic correlates of skewed mortality in infected Ccr7-deficient mice.