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-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.