期刊
JOURNAL OF IMMUNOLOGY
卷 187, 期 12, 页码 6437-6446出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1100499
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类别
资金
- Swedish Government
- Royal Physiographic Society in Lund
- Swedish Society of Medicine
- trusts of Emil and Wera Cornell
- Crafoord
- Ollie o Elof Ericksson
- Golje
- Thelma Zoega
- Alfred Osterlund
- Institut Pasteur
- INSERM
- Centre National de la Recherche Scientifique
- Association pour la Recherche sur le Cancer
Human group IIA-secreted phospholipase A(2) (sPLA(2)-IIA) is a bactericidal molecule important for the innate immune defense against Gram-positive bacteria. In this study, we analyzed its role in the host defense against Streptococcus pyogenes, a major human pathogen, and demonstrated that this bacterium has evolved a previously unidentified mechanism to resist killing by sPLA2-IIA. Analysis of a set of clinical isolates demonstrated that an similar to 500-fold higher concentration of sPLA(2)-IIA was required to kill S. pyogenes compared with strains of the group B Streptococcus, which previously were shown to be sensitive to sPLA(2)-IIA, indicating that S. pyogenes exhibits a high degree of resistance to sPLA2-IIA. We found that an S. pyogenes mutant lacking sortase A, a transpeptidase responsible for anchoring LPXTG proteins to the cell wall in Gram-positive bacteria, was significantly more sensitive (similar to 30-fold) to sPLA(2)-IIA compared with the parental strain, indicating that one or more LPXTG surface proteins protect S. pyogenes against sPLA(2)-IIA. Importantly, using transgenic mice expressing human sPLA(2)-IIA, we showed that the sortase A-mediated sPLA(2)-IIA resistance mechanism in S. pyogenes also occurs in vivo. Moreover, in this mouse model, we also showed that human sPLA(2)-IIA is important for the defense against lethal S. pyogenes infection. Thus, we demonstrated a novel mechanism by which a pathogenic bacterium can evade the bactericidal action of sPLA(2)-IIA and we showed that sPLA(2)-IIA contributes to the host defense against S. pyogenes infection. The Journal of Immunology, 2011, 187: 6437-6446.
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