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IL-4 instructs TH1 responses and resistance to Leishmania major in susceptible BALB/c mice.
Immunity to infection with intracellular pathogens is regulated by interleukin 12 (IL-12), which mediates protective T helper type 1 (TH1) responses, or IL-4, which induces TH2 cells and susceptibility. Paradoxically, we show here that when present during the initial activation of dendritic cells (DCs) by infectious agents, IL-4 instructed DCs to produce IL-12 and promote TH1 development. This TH1 response established resistance to Leishmania major in susceptible BALB/c mice. When present later, during the period of T cell priming, IL-4 induced TH2 differentiation and progressive leishmaniasis in resistant mice. Because immune responses developed via the consecutive activation of DCs and then T cells, the contrasting effects of IL-4 on DC development and T cell differentiation led to immune responses that had opposing functional phenotypes.
Animals, Antigens, Protozoan/immunology, Cell Differentiation/drug effects, Cells, Cultured/drug effects, Dendritic Cells/drug effects, Dendritic Cells/immunology, Genetic Predisposition to Disease, Immunity, Innate, Interleukin-12/physiology, Interleukin-12/secretion, Interleukin-4/pharmacology, Interleukin-4/physiology, Leishmania major/immunology, Leishmania major/physiology, Leishmaniasis, Cutaneous/immunology, Mice, Mice, Inbred BALB C, Ovalbumin/immunology, Protozoan Proteins/immunology, Receptors, Antigen, T-Cell, alpha-beta/immunology, Recombinant Proteins/pharmacology, Specific Pathogen-Free Organisms, Th1 Cells/cytology, Th1 Cells/immunology, Th2 Cells/cytology, Th2 Cells/immunology, Time Factors
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