| Literature DB >> 26651945 |
Stacey L Kolar1, Pierre Kyme1, Ching Wen Tseng1, Antoine Soliman1, Amber Kaplan2, Jiurong Liang3, Victor Nizet4, Dianhua Jiang5, Ramachandran Murali6, Moshe Arditi1, David M Underhill2, George Y Liu7.
Abstract
In response to tissue injury, hyaluronan (HA) polymers are cleaved by host hyaluronidases, generating small fragments that ligate Toll-like receptors (TLRs) to elicit inflammatory responses. Pathogenic bacteria such as group B Streptococcus (GBS) express and secrete hyaluronidases as a mechanism for tissue invasion, but it is not known how this activity relates to immune detection of HA. We found that bacterial hyaluronidases secreted by GBS and other Gram-positive pathogens degrade pro-inflammatory HA fragments to their component disaccharides. In addition, HA disaccharides block TLR2/4 signaling elicited by both host-derived HA fragments and other TLR2/4 ligands, including lipopolysaccharide. Application of GBS hyaluronidase or HA disaccharides reduced pulmonary pathology and pro-inflammatory cytokine levels in an acute lung injury model. We conclude that breakdown of host-generated pro-inflammatory HA fragments to disaccharides allows bacterial pathogens to evade immune detection and could be exploited as a strategy to treat inflammatory diseases.Entities:
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Year: 2015 PMID： 26651945 PMCID： PMC4683412 DOI： 10.1016/j.chom.2015.11.001
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023