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Cell Host Microbe. 2015 Dec 9;18(6):694-704. doi: 10.1016/j.chom.2015.11.001.

Group B Streptococcus Evades Host Immunity by Degrading Hyaluronan.

Author information

  • 1Division of Pediatric Infectious Diseases, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • 2Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • 3Division of Pulmonary, Department of Medicine, and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • 4Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA.
  • 5Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Division of Pulmonary, Department of Medicine, and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • 6Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • 7Division of Pediatric Infectious Diseases, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: george.liu@cshs.org.

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.

PMID:
26651945
PMCID:
PMC4683412
DOI:
10.1016/j.chom.2015.11.001
[PubMed - indexed for MEDLINE]
Free PMC Article
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