Nonopsonic binding of type III Group B Streptococci to human neutrophils induces interleukin-8 release mediated by the p38 mitogen-activated protein kinase pathway.
Nonopsonic interaction of host immune cells with pathogens is an important first line of defense. We hypothesized that nonopsonic recognition between type III group B streptococcus and human neutrophils would occur and that the interaction would be sufficient to trigger neutrophil activation. By using a serum-free system, it was found that heat-killed type III group B streptococci bound to neutrophils in a rapid, stable, and inoculum-dependent manner that did not result in ingestion. Transposon-derived type III strain COH1-13, which lacks capsular polysaccharide, and strain COH1-11 with capsular polysaccharide lacking terminal sialic acid demonstrated increased neutrophil binding, suggesting that capsular polysaccharide masks an underlying binding site. Experiments using monoclonal antibodies to complement receptor 1 and to the I domain or lectin site of complement receptor 3 did not inhibit binding, indicating that the complement receptors used for ingestion of opsonized group B streptococci were not required for nonopsonic binding. Nonopsonic binding resulted in rapid activation of cellular p38 and p44/42 mitogen-activated protein kinases. This interaction was not an effective trigger for superoxide production but did promote release of the proinflammatory cytokine interleukin-8. The release of interleukin-8 was markedly suppressed by the p38 mitogen-activated protein kinase inhibitor SB203580 but was only minimally suppressed by the mitogen-activated protein/extracellular signal-regulated kinase inhibitor PD98059. Thus, nonopsonic binding of type III group B streptococci to neutrophils is sufficient to initiate intracellular signaling pathways and could serve as an arm of innate immunity of particular importance to the immature host.
Albanyan
E A
EA
Sections of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Vallejo
J G
JG
Smith
C W
CW
Edwards
M S
MS
D000911:Antibodies, Monoclonal / Q000276:immunology; D001422:Bacterial Adhesion; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D008024:Ligands; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology; D009504:Neutrophils / Q000382:microbiology*; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis; D016897:Respiratory Burst; D013292:Streptococcus agalactiae / Q000502:physiology*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
D000911:Antibodies, Monoclonal; D016209:Interleukin-8; D008024:Ligands; D009895:Opsonin Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases