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-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.

• Authors: Miriam Rodriguez-Sosa, Lucia E Rosas, Luis I Terrazas, Bao Lu, Craig Gerard, Abhay R Satoskar
• Journal: Immunology and cell biology (Immunol Cell Biol) Vol. 81 Issue 2 Pg. 114-20 (Apr 2003) ISSN: 0818-9641 [Print] United States
• PMID: 12631234 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ccr1 protein, mouse
• Cytokines
• Immunoglobulin G
• Receptors, CCR1
• Receptors, Chemokine

Topics

• Animals
• Antibody Formation
• Cytokines (biosynthesis)
• Disease Susceptibility (immunology)
• Genetic Predisposition to Disease
• Immunity, Cellular
• Immunoglobulin G (blood)
• Leishmania major (immunology)
• Leishmaniasis, Cutaneous (immunology, pathology)
• Lymph Nodes (cytology, parasitology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Receptors, CCR1
• Receptors, Chemokine (genetics, immunology)
• Th2 Cells (immunology)
• Time Factors