Neutrophils play critical role for the type 2 protective responses against nematode parasite N. brasiliensis (51.5)

Abstract

Abstract Nippostrongylus brasiliensis (Nb) infection induces a potent Th2 response; however, little is known about the innate host-pathogen interactions that lead to the protective Th2 immunity. To identify these early events, microarray analysis was performed on draining skin lymph nodes shortly after Nb inoculation. Expression of several chemokines, including CCL2 and CXCR3 ligands, were found increased. We observed a transient and marked increase in Gr-1+ cells in the draining lymph node after Nb inoculation, which was CCL2-dependent. The Gr-1bright population was identified as neutrophils expressing TGFβ and TNFα. We further demonstrated that neutrophils were required for host protection against Nb infection and for the optimal Th2 development. After neutrophil depletion, Nb infection resulted in early IFN-γ expression, high mortality and delayed worm expulsion. Decreased Th2 cytokine expression and elevated serum IgG2a were also observed. In contrast, infection with Nb larvae treated with antibiotics cocktail to eliminate associated bacteria induced a protective Th2 response in neutrophil-depleted hosts. These studies suggest that the primary function of neutrophils in this model was to eliminate bacteria associated with parasite infection. Neutrophils thus play an essential role in depleting Th1-inducing bacteria, thereby promoting optimal development of the host protective Th2 response.