Faculty Publications

The TGF‐β Response to Leishmania chagasi in the Absence of IL‐12

Document Type

Article

Keywords

Cytokine, Dendritic cell, IL-12, Parasitic-protozoan infection, Vaccination

Journal/Book/Conference Title

European Journal of Immunology

Volume

32

Issue

12

First Page

3556

Last Page

3565

Abstract

Cure of leishmaniasis requires a type 1 immune response characterized by IFN-γ production. Leishmania major infection leads to a type 2 response suppressing cure of susceptible BALB/c mice, and L. major causes an exacerbated type 2 response in mouse strains with a gene knockout (KO) such that they lack IL-12p40 (IL-12KO mice). In contrast, type 1 responses are inhibited by TGF-β without Th2 cell expansion in BALB/c mice infected with L. chagasi. We questioned whether the type 2 or the TGF-β response would dominate during L. chagasi infection of IL-12KO mice. C57BL/6 mice developed self-resolving L. chagasi infection with abundant IFN-γ. In contrast, L. chagasi disease was exacerbated and IFN-γ was low in IL-12KO mice. Total TGF-β was significantly higher in IL-12KO than control C57BL/6 mice, but IL-4 and IL-10 levels were similar. TGF-β was further augmented in IL-12/ IFN-γ double-KO mice. Thus, in contrast to L. major, the TGF-β response was exacerbated whereas type 2 cells were not expanded during L. chagasi infection of IL-12KO mice. We conclude that L. chagasi has an inherent propensity to elicit a prominent TGF-β response that either suppresses, or is suppressed by, a type 1 response. We propose this be termed a "type 3" immune response, which can antagonize a type 1 response.

Department

Department of Biology

Original Publication Date

12-1-2002

DOI of published version

10.1002/1521-4141(200212)32:12<3556::AID-IMMU3556>3.0.CO;2-Q

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