Utilizing CX3CR1GFP/PGRPdsRed reporter mice to monitor myeloid and granulocyte responses during helminth infection (MPF6P.652)

Abstract

Abstract CX3CR1GFP/PGRPdsRed reporter mice have previously been used to monitor trafficking of monocytes and neutrophils, respectively. With this new tool, we examined myeloid cell and neutrophil behavior during murine infection with the helminth, Nippostrongylus brasiliensis (Nb). Nb acutely infects the lungs leading to significant infiltration of PGRPdsRed neutrophils and CX3CR1GFP monocytes compared to naïve mice. Using ex vivo time-lapse confocal microscopy, we discovered that Nb infection increased chemotaxis of CX3CR1GFP monocytes and PGRPdsRed neutrophils. Because CX3CR1GFP expression is a loss of function knock-in mutation, we tested the function of CX3CR1 in the immune response to Nb. After inoculation with infective larvae, CX3CR1GFP mice were less susceptible to infection compared to wild-type mice and had lower worm counts and parasite eggs in the feces. Additionally, ATP cell viability assay revealed that worms recovered from reporter mice were less viable than worms isolated from wild-type mice. Taken together, CX3CR1GFP/PGRPdsRed mice make it possible to monitor myeloid cell and neutrophil behavior, and reveal a previously unrecognized role for CX3CR1 in impairing Nb expulsion.