title: Deletion of the complement phagocytic receptors CR3 and CR4 does not alter susceptibility to experimental cerebral malaria.
abstract: Complement receptors for C3-derived fragments (CR1-4) play critical roles in innate and adaptive immune responses. Of these receptors, CR3 and CR4 are important in binding and phagocytosis of complement-opsonized pathogens including parasites. The role of CR3 and CR4 in malaria or in cerebral malaria (CM) has received little attention and remains poorly understood in both human disease and rodent models of malaria. CR3 and CR4 are members of the β(2) -integrin family of adhesion molecules and are expressed on all leucocytes that participate in the development of CM, most importantly as it relates to parasite phagocytosis (monocytes/macrophages) and antigen processing and presentation (dendritic cells). Thus, it is possible that these receptors might play an important role in disease development. To address this question, we examined the role of CR3(-/-)  and CR4(-/-)  in experimental cerebral malaria (ECM). We found that both CR3(-/-)  and CR4(-/-)  mice were fully susceptible to ECM and developed disease comparable to wild-type mice. Our results indicate that CR3 and CR4 are not critical to the pathogenesis of ECM despite their role in elimination of complement-opsonized pathogens. These findings support recent studies indicating the importance of the terminal complement pathway and the membrane attack complex in ECM pathogenesis.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: T N
authors.initials: TN
authors.lastname: Ramos
authors.forename: D C
authors.initials: DC
authors.lastname: Bullard
authors.forename: S R
authors.initials: SR
authors.lastname: Barnum
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D016167:Integrin alphaXbeta2 / Q000235:genetics*; D016177:Macrophage-1 Antigen / Q000235:genetics*; D016779:Malaria, Cerebral / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017384:Sequence Deletion
chemical_list: D016167:Integrin alphaXbeta2; D016177:Macrophage-1 Antigen