Chemokine production and leukocyte recruitment to the lungs of Paracoccidioides brasiliensis-infected mice is modulated by interferon-gamma.
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-gamma in the course of Paracoccidioides brasiliensis (Pb) infection in mice. We found an association between KC and MIP-1alpha (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-gamma (GKO mice) we observed increased production of KC and MIP-1alpha 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-gamma modulates the expression of chemokines and chemokine receptors as well as the kind of cells that infiltrate the lungs of Pb-infected mice.
Souto
Janeusa T
JT
Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Aliberti
Júlio C
JC
Campanelli
Ana P
AP
Livonesi
Márcia C
MC
Maffei
Cláudia M L
CM
Ferreira
Beatriz R
BR
Travassos
Luiz R
LR
Martinez
Roberto
R
Rossi
Marcos A
MA
Silva
João S
JS
D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology*; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010228:Paracoccidioides; D010229:Paracoccidioidomycosis / Q000276:immunology* / Q000473:pathology*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D018925:Chemokines; D019707:Receptors, Chemokine; D007371:Interferon-gamma