Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Protozoan / immunology
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Cell Differentiation / drug effects
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Cells, Cultured / drug effects
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Dendritic Cells / drug effects*
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Genetic Predisposition to Disease
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Immunity, Innate
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Interleukin-12 / metabolism
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Interleukin-12 / physiology
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Interleukin-4 / pharmacology
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Interleukin-4 / physiology*
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Leishmania major / immunology*
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Leishmania major / physiology
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Leishmaniasis, Cutaneous / immunology*
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Mice
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Mice, Inbred BALB C
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Ovalbumin / immunology
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Protozoan Proteins / immunology
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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Recombinant Proteins / pharmacology
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Specific Pathogen-Free Organisms
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Th1 Cells / cytology
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Th1 Cells / immunology*
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Th2 Cells / cytology
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Th2 Cells / immunology
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Time Factors
Substances
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Antigens, Protozoan
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Protozoan Proteins
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Receptors, Antigen, T-Cell, alpha-beta
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Recombinant Proteins
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LACK antigen, Leishmania
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Interleukin-12
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Interleukin-4
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Ovalbumin