Secreted Group IIA Phospholipase A2 Protects Humans Against the Group B Streptococcus: Experimental and Clinical Evidence.

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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.

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  • Infectious Medicine
Original languageEnglish
Pages (from-to)2025-2035
JournalJournal of Infectious Diseases
Volume208
Issue number12
Publication statusPublished - 2013
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division of Medical Microbiology (013250400), Division of Infection Medicine (SUS) (013008000)