CXCR3-/- mice mount an efficient Th1 response but fail to control Leishmania major infection.
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.
Rosas
Lucia E
LE
Department of Microbiology, The Ohio State University, Columbus, Ohio 43221, USA.
Barbi
Joseph
J
Lu
Bao
B
Fujiwara
Yuko
Y
Gerard
Craig
C
Sanders
Virginia M
VM
Satoskar
Abhay R
AR
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
C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine