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Germ-free mice produce high levels of interferon-gamma in response to infection with Leishmania major but fail to heal lesions

Published online by Cambridge University Press:  28 June 2005

M. R. OLIVEIRA
Affiliation:
Departamento de Parasitologia, ICB, Universidade Federal de Minas Gerais, CP486, 30161-970, Belo Horizonte, MG, Brazil Departamento de Biologia Molecular, CCEN, Universidade Federal da Paraíba, Campus I. 58059-900, João Pessoa, PB, Brazil
W. L. TAFURI
Affiliation:
Departamento de Patologia Geral, Universidade Federal de Minas Gerais, CP486, 30161-970, Belo Horizonte, MG, Brazil
L. C. C. AFONSO
Affiliation:
Departamento de Ciências Biológicas/NUPEB, ICEB, Universidade Federal de Ouro Preto, Campus Universitário Morro do Cruzeiro, 35400-000, Ouro Preto, MG, Brazil
M. A. P. OLIVEIRA
Affiliation:
Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, CP486, 30161-970, Belo Horizonte, MG, Brazil current address: Instituto de Patologia Tropical e Saúde Pública/ DMIPP, Universidade Federal de Goiás, 74605-050, Goiânia, GO, Brazil
J. R. NICOLI
Affiliation:
Departamento de Microbiologia, Universidade Federal de Minas Gerais, CP486, 30161-970, Belo Horizonte, MG, Brazil
E. C. VIEIRA
Affiliation:
Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, CP486, 30161-970, Belo Horizonte, MG, Brazil
P. SCOTT
Affiliation:
Department of Pathobiology, School of Veterinary Medicine, 3800 Spruce Street, University of Pennsylvania, Philadelphia, PA, 19104, USA
M. N. MELO
Affiliation:
Departamento de Parasitologia, ICB, Universidade Federal de Minas Gerais, CP486, 30161-970, Belo Horizonte, MG, Brazil
L. Q. VIEIRA
Affiliation:
Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, CP486, 30161-970, Belo Horizonte, MG, Brazil

Abstract

In order to investigate the importance of the host microbiota on differentiation of T cell subsets in response to infection, Swiss/NIH germ-free mice and conventional (microbiota-bearing) mice were infected with Leishmania major, and lesion development, parasite loads, and cytokine production were assessed. Germ-free mice failed to heal lesions and presented a higher number of parasites at the site of infection than their conventional counterparts. In addition, histopathological analysis indicated a higher density of parasitized macrophages in lesions from germ-free mice than in conventional mice. The initial production of interleukin (IL)-12 and interferon-gamma (IFN-γ) in germ-free mice was comparable to the conventional controls. Also, germ-free mice produced elevated levels of IFN-γ and lower levels of IL-4 throughout the course of infection, suggesting the development of a Th1 response. Macrophages from germ-free mice exposed to IFN-γ and infected with amastigotes in vitro were not as efficient at killing parasites as macrophages from conventional animals. These observations indicate that the microbiota is not essential for the development of Th1 immune responses, but seems to be important for macrophage activation.

Type
Research Article
Copyright
© 2005 Cambridge University Press

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