title: CXCR3-/- mice mount an efficient Th1 response but fail to control Leishmania major infection.
abstract: Chemokines play a critical role in recruitment of leukocytes to the site of infection, which is essential for host defense. We analyzed the role of CXC chemokine receptor 3 (CXCR3) in the control of cutaneous leishmaniasis using CXCR3-/- C57BL/6 mice. We found that Leishmania major-infected CXCR3-/- mice mount an efficient Th1 response as evident by markedly increased serum levels of Th1-associated IgG2a and significant production of IFN-gamma and IL-12 by the draining lymph node cells, restrict systemic spread of infection, but fail to control parasite replication at the site of infection and develop chronic non-healing lesions. Furthermore, the inability of CXCR3-/- mice to control cutaneous L. major growth was associated with fewer CD4+ and CD8+ T cells and significantly lower levels of IFN-gamma in their lesions as compared to CXCR3+/+ mice. These results demonstrate that CXCR3 plays a critical role in the host defense against cutaneous leishmaniasis caused by L. major. Furthermore, they also suggest that the susceptibility of CXCR3-/- mice to L. major is due to impaired CD4+ and CD8+ T cell trafficking and decreased production of IFN-gamma at the site of infection rather than to their inability to mount a parasite-specific Th1 response.
authors.affiliation: Department of Microbiology, The Ohio State University, Columbus, Ohio 43221, USA.
authors.forename: Lucia E
authors.initials: LE
authors.lastname: Rosas
authors.forename: Joseph
authors.initials: J
authors.lastname: Barbi
authors.forename: Bao
authors.initials: B
authors.lastname: Lu
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Craig
authors.initials: C
authors.lastname: Gerard
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Sanders
authors.forename: Abhay R
authors.initials: AR
authors.lastname: Satoskar
mesh_terms: D000818:Animals; D005528:Foot / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000469:parasitology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine