A macrophage invasion mechanism of pathogenic mycobacteria.
Tuberculosis is the leading cause of death due to an infectious organism, killing an estimated 3 million people annually. Mycobacterium tuberculosis, the causative agent of tuberculosis, and other pathogenic mycobacteria require entry into host macrophages to initiate infection. An invasion mechanism was defined that was shared among pathogenic mycobacteria including M. tuberculosis, M. leprae, and M. avium but not by nonpathogenic mycobacteria or nonmycobacterial intramacrophage pathogens. This pathway required the association of the complement cleavage product C2a with mycobacteria resulting in the formation of a C3 convertase. The mycobacteria-associated C2a cleaved C3, resulting in C3b opsonization of the mycobacteria and recognition by macrophages.
Schorey
J S
JS
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Carroll
M C
MC
Brown
E J
EJ
D000595:Amino Acid Sequence; D000818:Animals; D003175:Complement C2 / Q000502:physiology*; D050678:Complement C2a; D003176:Complement C3 / Q000378:metabolism; D050577:Complement C3-C5 Convertases / Q000378:metabolism; D003179:Complement C3b / Q000276:immunology; D006736:Horses; D006801:Humans; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000472:pathogenicity*; D015269:Mycobacterium avium Complex / Q000276:immunology / Q000472:pathogenicity*; D009163:Mycobacterium bovis / Q000276:immunology / Q000472:pathogenicity; D009166:Mycobacterium leprae / Q000276:immunology / Q000472:pathogenicity; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D009895:Opsonin Proteins; D014774:Virulence
D003175:Complement C2; D003176:Complement C3; D009895:Opsonin Proteins; D007531:Isoflurophate; D003179:Complement C3b; D050577:Complement C3-C5 Convertases; D050678:Complement C2a