"The TGF‐β Response to Leishmania chagasi in the Absence of IL‐12" by Nilda E. Rodriguez, Mary E. Wilson et al.
 

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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