CC chemokine receptor 1 enhances susceptibility to Leishmania major during early phase of infection.
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-gamma, 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-gamma 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.
Rodriguez-Sosa
Miriam
M
Departments of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Microbiology, The Ohio State University, Columbus, Ohio 43210, USA.
Rosas
Lucia E
LE
Terrazas
Luis I
LI
Lu
Bao
B
Gerard
Craig
C
Satoskar
Abhay R
AR
D000818:Animals; D000917:Antibody Formation; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors
C515301:Ccr1 protein, mouse; D016207:Cytokines; D007074:Immunoglobulin G; D054389:Receptors, CCR1; D019707:Receptors, Chemokine