The Importance of TGF-β in Murine Visceral Leishmaniasis

Mary E Wilson; Betty M Young; Beverly L Davidson; Kimberly A Mente; Stephen E McGowan

doi:10.4049/jimmunol.161.11.6148

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The Importance of TGF-β in Murine Visceral Leishmaniasis

Journal article

Peer reviewed

The Importance of TGF-β in Murine Visceral Leishmaniasis

Mary E Wilson, Betty M Young, Beverly L Davidson, Kimberly A Mente and Stephen E McGowan

The Journal of immunology (1950), Vol.161(11), pp.6148-6155

12/01/1998

DOI: 10.4049/jimmunol.161.11.6148

PMID: 9834100

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Abstract

IFN-γ is critical for the cure of leishmaniasis in humans and mice. BALB/c mice are genetically susceptible to infection with the visceralizing species of Leishmania, L. chagasi. We have evidence that a soluble factor(s) inhibits IFN-γ production by cultured liver granuloma cells from BALB/c mice during L. chagasi infection. In contrast, liver granulomas from C3H.HeJ mice, which are genetically resistant to L. chagasi infection, produce abundant IFN-γ. According to ELISAs and neutralization studies, there was not evidence that the Th2-type cytokines IL-10 or IL-4 contributed to IFN-γ suppression. However, both Ab neutralization and immunohistochemistry showed that granuloma-derived TGF-β was, at least in part, responsible for inhibiting IFN-γ release by CD4+ cells in BALB/c liver granuloma cultures. Consistently, TGF-β levels were high in liver granulomas from susceptible BALB/c mice but low in resistant C3H mice or in BALB/c mice that were immunized against L. chagasi disease. Administration of recombinant adenovirus expressing TGF-β (AdV-TGFβ) but not IL-10 (AdV-IL10) caused genetically resistant C3H mice to become significantly more susceptible to L. chagasi infection. In contrast, either AdV-TGFβ or AdV-IL10 could abrogate the protective immune response achieved by immunization of BALB/c mice. We conclude that locally secreted TGF-β inhibits Th1-associated cure of murine visceral leishmaniasis caused by L. chagasi, independently of Th2-type cytokines.

Antigens, Protozoan - immunology

Granuloma - metabolism

Genetic Vectors - administration & dosage

Vaccination

Liver Diseases, Parasitic - immunology

Leishmaniasis, Visceral - immunology

Transforming Growth Factor beta - biosynthesis

Antigens, Protozoan - pharmacology

Liver Diseases, Parasitic - metabolism

Interferon-gamma - antagonists & inhibitors

Adenoviridae - genetics

Disease Models, Animal

Transforming Growth Factor beta - immunology

Genetic Vectors - immunology

Cells, Cultured

Cytokines - secretion

Solubility

Transforming Growth Factor beta - physiology

Leishmaniasis, Visceral - metabolism

Leishmaniasis, Visceral - pathology

Mice, Inbred C3H

Animals

Leishmania infantum - immunology

Granuloma - immunology

Interleukin-10 - biosynthesis

Mice

Mice, Inbred BALB C

Kinetics

Cytokines - biosynthesis

Interferon-gamma - biosynthesis

Details

Title: Subtitle: The Importance of TGF-β in Murine Visceral Leishmaniasis
Creators: Mary E Wilson - Department of Internal Medicine, University of Iowa, Veterans Affairs Medical Center, Iowa City 52242, USA
Betty M Young
Beverly L Davidson
Kimberly A Mente
Stephen E McGowan
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.161(11), pp.6148-6155
DOI: 10.4049/jimmunol.161.11.6148
PMID: 9834100
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: DK/AI52550 / NIDDK NIH HHS HL45135 / NHLBI NIH HHS AI32135 / NIAID NIH HHS
Language: English
Date published: 12/01/1998
Academic Unit: Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
Record Identifier: 9983984517302771

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