Chemokine production and leukocyte recruitment to the lungs of Paracoccidioides brasiliensis-infected mice is modulated by interferon-gamma

Am J Pathol. 2003 Aug;163(2):583-90. doi: 10.1016/s0002-9440(10)63686-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Humans
  • Interferon-gamma / immunology*
  • Interferon-gamma / metabolism
  • Leukocytes / physiology*
  • Lung / immunology*
  • Lung / microbiology
  • Lung / pathology
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Mice
  • Mice, Knockout
  • Paracoccidioides
  • Paracoccidioidomycosis / immunology*
  • Paracoccidioidomycosis / pathology*
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism
  • Th1 Cells / immunology
  • Th1 Cells / metabolism


  • Chemokines
  • Receptors, Chemokine
  • Interferon-gamma