CC chemokine receptor 1 enhances susceptibility to Leishmania major during early phase of infection

Abstract

CC chemokine receptor 1 (CCR1) is expressed on the surfaces of monocytes, lymphocytes, neutrophils and eosinophils. CC chemokine receptor 1 not only regulates leucocyte chemotaxis, but also plays a role in the regulation of Th1/Th2 cytokine responses. To determine the role of CCR1 in regulation of immune response during Leishmania major infection, we analysed the course of cutaneous L. major infection in CCR1‐deficient C57BL/6 mice (CCR1−/−) and compared with similarly infected wild‐type mice (CCR1+/+). Following L. major infection, CCR1−/− mice developed significantly smaller lesions containing fewer parasites than CCR1+/+ mice. Furthermore, the severity of the inflammation as assessed by the degree of leucocyte infiltration at the site of infection was similar in CCR1+/+ and CCR1−/− mice. Although both groups developed significant antibody responses following L. major infection, CCR1−/− mice produced significantly lower IgE. On day 20 postinfection, LmAg‐stimulated lymph node cells from L. major‐infected CCR1+/+ and CCR1−/− mice produced comparable levels of IL‐12 and IFN‐γ, but those from CCR1−/− mice produced significantly less IL‐4 and IL‐10. By day 70, lymph node cells from both CCR1+/+ and CCR1−/− mice produced significant amounts of IL‐12 and IFN‐γ but low IL‐4. At both time points, the draining lymph nodes from CCR1+/+ and CCR1−/− mice contained similar number of leucocytes. These results demonstrate that CCR1 plays a role in pathogenesis of cutaneous L. major infection. Moreover, they also indicate that CCR1 exacerbates L. major infection in C57BL/6 mice by up‐regulating Th2‐like response rather than inhibiting Th1 development or/and influencing leucocyte chemotaxis.