title: Secreted group IIA phospholipase A2 protects humans against the group B streptococcus: experimental and clinical evidence.
abstract: Group B streptococcus (GBS) is a leading neonatal pathogen and a growing cause of invasive disease in the elderly, with clinical manifestations such as pneumonia and sepsis. Despite its clinical importance, little is known about innate immunity against GBS in humans. Here, we analyze the role of human group IIA secreted phospholipase A2 (sPLA2-IIA), a bactericidal enzyme induced during acute inflammation, in innate immunity against GBS. We show that clinical GBS isolates are highly sensitive to killing by sPLA2-IIA but not by human antimicrobial peptides. Using transgenic mice that express human sPLA2-IIA, we demonstrate that this enzyme is crucial for host protection against systemic infection and lung challenge by GBS. We found that acute sera from humans diagnosed with invasive GBS disease contain increased levels of sPLA2-IIA compared with normal sera from healthy individuals, indicating that GBS induces an sPLA2-IIA response in blood during human infection. We demonstrate that clinically relevant GBS strains are rapidly killed in these acute sera. We also demonstrate that the bactericidal effect is entirely due to sPLA2-IIA, showing that sPLA2-IIA might represent an important component of humoral innate immunity against GBS. Our data provide experimental and clinical evidence that sPLA2-IIA protects humans against GBS infections.
authors.affiliation: Department of Laboratory Medicine, Division of Medical Microbiology, Lund University, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Movert
authors.forename: Yongzheng
authors.initials: Y
authors.lastname: Wu
authors.forename: Gérard
authors.initials: G
authors.lastname: Lambeau
authors.forename: Fredrik
authors.initials: F
authors.lastname: Kahn
authors.forename: Lhousseine
authors.initials: L
authors.lastname: Touqui
authors.forename: Thomas
authors.initials: T
authors.lastname: Areschoug
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D005260:Female; D054501:Group II Phospholipases A2 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007231:Infant, Newborn; D008171:Lung Diseases; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D013290:Streptococcal Infections / Q000097:blood / Q000201:enzymology* / Q000382:microbiology*; D013292:Streptococcus agalactiae / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054501:Group II Phospholipases A2
keywords: antimicrobial molecules; bactericidal; group B streptococcus; innate immunity