The TGF-β response toLeishmania chagasi in the absence of IL-12

Mary E Wilson; Thomas J Recker; Nilda E Rodriguez; Betty M Young; Kindra K Burnell; Judy A Streit; Joel N Kline

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

Back

The TGF-β response toLeishmania chagasi in the absence of IL-12

Journal article

Peer reviewed

The TGF-β response toLeishmania chagasi in the absence of IL-12

Mary E Wilson, Thomas J Recker, Nilda E Rodriguez, Betty M Young, Kindra K Burnell, Judy A Streit and Joel N Kline

European journal of immunology, Vol.32(12), pp.3556-3565

12/2002

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

PMID: 12516540

View Online

Abstract

Cure of leishmaniasis requires a type 1 immune response characterized by IFN-gamma 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-beta without Th2 cell expansion in BALB/c mice infected with L. chagasi. We questioned whether the type 2 or the TGF-beta response would dominate during L. chagasi infection of IL-12KO mice. C57BL/6 mice developed self-resolving L. chagasi infection with abundant IFN-gamma. In contrast, L. chagasi disease was exacerbated and IFN-gamma was low in IL-12KO mice. Total TGF-beta was significantly higher in IL-12KO than control C57BL/6 mice, but IL-4 and IL-10 levels were similar. TGF-beta was further augmented in IL-12/IFN-gamma double-KO mice. Thus, in contrast to L. major, the TGF-beta 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-beta 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.

Interleukin-12 - deficiency

Interleukin-12 - genetics

Dendritic Cells - immunology

Mice, Inbred C57BL

Leishmaniasis, Visceral - immunology

Th2 Cells - immunology

Th1 Cells - immunology

Transforming Growth Factor beta - biosynthesis

Mice, Knockout

Interleukin-4 - biosynthesis

Animals

Immunization, Passive

Leishmania infantum - immunology

Interleukin-10 - biosynthesis

Mice

Interferon-gamma - genetics

Interferon-gamma - deficiency

Details

Title: Subtitle: The TGF-β response toLeishmania chagasi in the absence of IL-12
Creators: Mary E Wilson - Veterans' Affairs Medical Center, Department of Internal Medicine, University of Iowa, Iowa City 52242, USA. mary-wilson@uiowa.edu
Thomas J Recker
Nilda E Rodriguez
Betty M Young
Kindra K Burnell
Judy A Streit
Joel N Kline
Resource Type: Journal article
Publication Details: European journal of immunology, Vol.32(12), pp.3556-3565
DOI: 10.1002/1521-4141(200212)32:12<3556::AID-IMMU3556>3.0.CO;2-Q
PMID: 12516540
NLM abbreviation: Eur J Immunol
ISSN: 0014-2980
eISSN: 1521-4141
Publisher: Germany
Grant note: R01 AI45540 / NIAID NIH HHS HL59324 / NHLBI NIH HHS R03 TW01369 / FIC NIH HHS R01 AI48822 / NIAID NIH HHS
Language: English
Date published: 12/2002
Academic Unit: Microbiology and Immunology; Occupational and Environmental Health; International Programs; Epidemiology; Internal Medicine
Record Identifier: 9984001135002771

Metrics

21 Record Views

34 Times Cited - Web of Science