CXCR3–/– mice mount an efficient Th1 response but fail to control Leishmania major infection

AbstractChemokines 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‐γ 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‐γ 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‐γ at the site of infection rather than to their inability to mount a parasite‐specific Th1 response.