title: Interferon-γ influences the composition of leukocytic infiltrates in murine lyme carditis.
abstract: Interferon (IFN)-γ is present in lesions of patients with Lyme disease and positively correlates with the severity of manifestations. To investigate the role of IFNγ in the development of Lyme carditis, wild-type and IFNγ-deficient C57BL/6 mice were infected with the causative bacterium, Borrelia burgdorferi. Histological analysis revealed no change in the severity of carditis between wild-type and IFNγ-deficient mice at 14, 21, 25, and 28 days after infection. However, a distinct shift in the types of leukocytes within the hearts of IFNγ-deficient mice was observed at 25 days. In the absence of IFNγ, the number of neutrophils in the heart was increased, whereas the number of T lymphocytes was decreased. Bacterial loads within hearts were the same as in wild-type mice. Macrophages secrete chemokines that recruit immune cells, which could contribute to the accumulation of leukocytes in murine Lyme carditis. The ability of IFNγ and B. burgdorferi to activate murine macrophages was examined, and the two stimuli synergistically induced chemoattractants for mononuclear cells (ie, CXCL9, CXCL10, CXCL11, CXCL16, and CCL12) and decreased those for neutrophils (ie, CXCL1, CXCL2, and CXCL3). IFNγ and B. burgdorferi also synergistically enhanced secretion of CXCL9 and CXCL10 by murine cardiac endothelial cells. These results indicate that IFNγ influences the composition of inflammatory infiltrates in Lyme carditis by promoting the accumulation of leukocytes associated with chronic inflammation and suppressing that of cells that typify acute inflammation.
authors.affiliation: Graduate Program in Molecular and Cellular Biology, School of Medicine, Stony Brook University, Stony Brook, NY 11794-5120, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Sabino
authors.forename: Sonya J
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Shane C
authors.initials: SC
authors.lastname: McAllister
authors.forename: Patricio
authors.initials: P
authors.lastname: Mena
authors.forename: Martha B
authors.initials: MB
authors.lastname: Furie
mesh_terms: D000818:Animals; D025065:Borrelia burgdorferi / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D005786:Gene Expression Regulation / Q000187:drug effects; D007371:Interferon-gamma / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology*; D008193:Lyme Disease / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D018925:Chemokines; D007371:Interferon-gamma