Patterns of chemokine expression in models of Schistosoma mansoni inflammation and infection reveal relationships between type 1 and type 2 responsesand chemokines in vivo

To explore the roles of chemokines in type 1 and type 2 responses in vivo, we examined mRNA expression for a panel of up to 17 chemokines in experimen tal mouse models using Schistosoma mansoni. These studies revealed that Mig (monokine induced by gamma interferon), cytokine-responsive gene 2/10-kDa interferon-inducible protein, RANTES, lymphotactin, macrophage inflammatory protein 1 beta (MIP-1 beta), JE/monocyte chemoattractant protein 1, and MI P-2 are associated with type 1 egg-induced responses and that thymus-derive d chemotactic agent 3 (TCA3), eotaxin, MIP-1 alpha, and MIP-1 gamma are ass ociated with type 2 egg-induced responses. After cercarial infection, both type 1-associated and type 2-associated chemokines were elevated in the liv ers of infected mice presensitized with eggs and recombinant interieukin-12 (rIL-12), a regimen that diminishes pathology. Neutralization of IL-12 or gamma interferon during egg deposition reversed the effects of prior treatm ent with rIL-12, leading to a return to larger granulomas; persistently ele vated expression of TCA3, eotaxin, and MIP-1 alpha; and a marked reduction in the expression of type 1-associated chemokines despite the maintenance o f a dominant type 1 cytokine response in the draining lymph nodes. Our find ings suggest that there are patterns of coordinate chemokine expression cha racteristic of type 1 and type 2 responses in vivo; that the cells recruite d by a given pattern of chemokines may differ, depending on the composition of peripheral populations; and that patterns of tissue expression of chemo kines may determine the character of an inflammatory response independently of the dominant pattern of differentiation of antigen-specific T cells. Ou r data reveal new relationships between chemokines and polarized immune res ponses and suggest that end organ inflammation might be altered by chemokin e blockade without necessitating reversal of the phenotype of the majority of differentiated T cells.