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Infect Immun, February 1998, p. 800-806, Vol. 66, No. 2
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Protective Role of Gamma Interferon in Experimental Pulmonary Paracoccidioidomycosis

Luz E. Cano,dagger Suely S. Kashino, Celina Arruda, Denise André, Cynthia F. Xidieh, Lucia M. Singer-Vermes, Celidéia A. C. Vaz, Eva Burger, and Vera L. G. Calich*

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-gamma ). To better characterize this model, we measured type 1 and type 2 cytokines in the lungs and investigated the effect of endogenous IFN-gamma 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-gamma , interleukin-4 (IL-4), IL-5, and IL-10 higher than those in resistant mice. In both mouse strains, neutralization of endogenous IFN-gamma 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-gamma 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-gamma 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.

dagger Present address: Laboratório de Micologia Experimental, Corporación para Investigaciones Biológicas, Medellín, Colombia.




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