Complement receptor 3 deficiency influences lesion progression during Leishmania major infection in BALB/c mice.
Leishmania major is an obligately intracellular protozoan parasite that causes cutaneous leishmaniasis. Like numerous intracellular pathogens, Leishmania exploits cell surface receptors as a means of entry into host cells. Complement receptor 3 (CR3; also called CD11b/CD18), a beta(2) integrin on phagocytic cells, is one such receptor. Ligation of CR3 has been shown to inhibit the production of interleukin-12, the cytokine that is pivotal in establishing the cell-mediated response necessary to combat intracellular infection. Here we investigate the role that CR3 plays in the establishment and progression of cutaneous leishmaniaisis in vivo. Dermal lesions of wild-type BALB/c mice are characteristically progressive and lead to extensive tissue necrosis coupled with elevated parasite burdens; CD11b-deficient BALB/c mice, however, demonstrate an intermediate phenotype characterized by chronic lesions and a reduced incidence of tissue damage. Infection followed by a reinfection challenge indicates that both susceptible (BALB/c) and resistant (C57BL/6) mice, regardless of CD11b status, develop resistance to L. major. In addition, CD11b does not bias the T helper cytokine response to L. major infection. Our results further indicate that CD11b is not necessary for disease resolution in resistant mice; rather, this protein appears to play a minor role in susceptibility.
Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana 46556, USA.
Cristina R
CR
Carter
James P
JP
Whitcomb
Jessica A
JA
Campbell
Rami M
RM
Mukbel
Mary Ann
MA
McDowell
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D039481:CD11b Antigen / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D018320:Leishmania major / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000469:parasitology* / Q000473:pathology*; D007962:Leukocytes / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012720:Severity of Illness Index; D012867:Skin / Q000469:parasitology / Q000473:pathology
D000913:Antibodies, Protozoan; D039481:CD11b Antigen; D016207:Cytokines; D016177:Macrophage-1 Antigen