Critical role for complement receptor 3 (CD11b/CD18), but not for Fc receptors, in killing of Streptococcus pyogenes by neutrophils in human immune serum.
During phagocytosis, surface receptors on neutrophils interact with pathogens opsonized with complement factor C3b/iC3b and in some cases with antibodies. In human immune sera antibodies directed against surface-bound M proteins mediated killing of Streptococcus pyogenes by neutrophils. Surprisingly, blocking of the Fc receptors had little effect on the killing. In contrast, inhibition of C3b/iC3b generation, or blocking of the major neutrophil iC3b receptor CD11b/CD18, enabled S. pyogenes to grow efficiently in immune sera. Inhibition of CD11b/CD18, but not of CD32, the major neutrophil signaling Fc receptor, prevented Streptococcus-induced NADPH oxidase-dependent respiratory burst, and blocking of C3b/iC3b formation inhibited Streptococcus-induced activation of Cdc42, a small GTPase critically involved in transmitting pro-inflammatory signals to the cytoskeleton. Consequently, ligation of CD11b/CD18 by bacteria-bound iC3b is necessary for inducing a neutrophil response leading to elimination of S. pyogenes in immune human serum.
Nilsson
Maria
M
Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden. maria.nilsson@mig.lu.se
Weineisen
Maria
M
Andersson
Tommy
T
Truedsson
Lennart
L
Sjöbring
Ulf
U
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology*; D003179:Complement C3b / Q000276:immunology; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D017463:Receptors, Complement 3b / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology*
D000907:Antibodies, Bacterial; D039481:CD11b Antigen; D006023:Glycoproteins; D017463:Receptors, Complement 3b; D011961:Receptors, Fc; D011994:Recombinant Proteins; C023587:protein M (glycoprotein); D003179:Complement C3b