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(American Journal of Pathology. 2003;163:583-590.)
© 2003 American Society for Investigative Pathology

Chemokine Production and Leukocyte Recruitment to the Lungs of Paracoccidioides brasiliensis-Infected Mice Is Modulated by Interferon-

Janeusa T. Souto^*||, Júlio C. Aliberti^**, Ana P. Campanelli^*, Márcia C. Livonesi^*, Cláudia M.L. Maffei, Beatriz R. Ferreira^*, Luiz R. Travassos^¶, Roberto Martinez, Marcos A. Rossi and João S. Silva^*

From the Department of Biochemistry and Immunology,^* Cell Biology, Pathology, and Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; the Department of Microbiology, Immunology and Parasitology,^¶ Federal University of São Paulo, São Paulo, Brazil; Department of Microbiology and Parasitology,|| Federal University of Rio Grande do Norte, Natal, RN, Brazil; and the Immunobiology Section,^** Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

Chemokines and chemokine receptors play a role in cell recruitment during granulomatous inflammatory reactions. Here, we evaluated the expression of chemokines and chemokine receptors and their regulation by IFN- in the course of Paracoccidioides brasiliensis (Pb) infection in mice. We found an association between KC and MIP-1 (CCL3) production and neutrophil infiltration in the lungs of Pb-infected mice during the early acute phase of infection. High levels of RANTES/CCL5, MCP-1/CCL2, IP-10/CXCL10, and Mig/CXCL9 simultaneously with mononuclear cell infiltration in the lungs was found. In the absence of IFN- (GKO mice) we observed increased production of KC and MIP-1 and chronic neutrophilia. Moreover, we found a change in the chemokine receptor profiles expressed by wild-type (WT) versus GKO animals. Increased expression of CXCR3 and CCR5, and low levels of CCR3 and CCR4 were observed in the lungs of Pb-infected WT mice, whereas the opposite effect was observed in the lungs of GKO mice. Consistent with these results, infected cells from WT mice preferentially migrated in response to IP-10 (CXCR3 ligand), while those from GKO mice migrated in response to eotaxin/CCL11 (CCR3 ligand). These results suggest that IFN- modulates the expression of chemokines and chemokine receptors as well as the kind of cells that infiltrate the lungs of Pb-infected mice.

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