Complement receptor 3 deficiency influences lesion progression during Leishmania major infection in BALB/c mice

Infect Immun. 2009 Dec;77(12):5668-75. doi: 10.1128/IAI.00802-08. Epub 2009 Sep 21.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / blood
  • CD11b Antigen / genetics
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Disease Susceptibility
  • Female
  • Leishmania major / pathogenicity*
  • Leishmaniasis, Cutaneous / parasitology*
  • Leishmaniasis, Cutaneous / pathology*
  • Leukocytes / immunology
  • Macrophage-1 Antigen / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Severity of Illness Index
  • Skin / parasitology
  • Skin / pathology

Substances

  • Antibodies, Protozoan
  • CD11b Antigen
  • Cytokines
  • Macrophage-1 Antigen