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Infect Immun, February 1998, p. 800-806, Vol. 66, No. 2
Departamento de Imunologia, Instituto de
Ciências Biomédicas da Universidade de São Paulo,
São Paulo, Brazil
Received 14 April 1997/Returned for modification 21 May
1997/Accepted 23 October 1997
We have developed a murine model of pulmonary infection by
Paracoccidioides brasiliensis in which resistance was
associated with immunological activities governed by gamma interferon
(IFN-
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Protective Role of Gamma Interferon in Experimental
Pulmonary Paracoccidioidomycosis

). To better characterize this model, we measured type 1 and
type 2 cytokines in the lungs and investigated the effect of endogenous IFN-
depletion by monoclonal antibodies in the course of infection of susceptible (B10.A) and resistant (A/Sn) mice. At weeks 4 and 8 after infection, lungs from susceptible animals presented levels of
IFN-
, interleukin-4 (IL-4), IL-5, and IL-10 higher than those in
resistant mice. In both mouse strains, neutralization of endogenous IFN-
induced exacerbation of the pulmonary infection, earlier fungal
dissemination to the liver and spleen, impairment of the specific
cellular immune response resulting in significantly lower delayed-type
hypersensitivity reactions, and increased levels of immunoglobulin G1
(IgG1)- and IgG2b-specific antibodies. Histopathological analysis
demonstrated that depletion of IFN-
changes the focal granulomatous
lesions found in the lungs of B10.A and A/Sn mice into coalescent
granulomata which destroy the pulmonary architecture. These results
suggest that irrespective of the mouse strain, IFN-
plays a
protective role and that this cytokine is one major mediator of
resistance against P. brasiliensis infection in mice.
*
Corresponding author. Mailing address: Depto. de
Imunologia, Instituto de Ciências Biomédicas, Universidade
de São Paulo, Av. Prof. Lineu Prestes 2415, Cep 05508-009, São Paulo, SP, Brazil. Phone: 55-11-818 7397. Fax: 55-11-818 7224. E-mail: vlcalich{at}biomed.icb2.usp.br.
Present address: Laboratório de Micologia Experimental,
Corporación para Investigaciones Biológicas,
Medellín, Colombia.
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