B族链球菌通过降解透明质酸逃避宿主免疫。
Group B Streptococcus Evades Host Immunity by Degrading Hyaluronan.
作者信息
Kolar Stacey L, Kyme Pierre, Tseng Ching Wen, Soliman Antoine, Kaplan Amber, Liang Jiurong, Nizet Victor, Jiang Dianhua, Murali Ramachandran, Arditi Moshe, Underhill David M, Liu George Y
机构信息
Division 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.
Research 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.
出版信息
Cell Host Microbe. 2015 Dec 9;18(6):694-704. doi: 10.1016/j.chom.2015.11.001.
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.
针对组织损伤，宿主透明质酸酶会切割透明质酸（HA）聚合物，产生小片段，这些小片段会连接Toll样受体（TLR）以引发炎症反应。诸如B族链球菌（GBS）等致病细菌表达并分泌透明质酸酶作为组织入侵机制，但尚不清楚这种活性与HA的免疫检测有何关系。我们发现GBS和其他革兰氏阳性病原体分泌的细菌透明质酸酶将促炎性HA片段降解为其组成二糖。此外，HA二糖可阻断宿主来源的HA片段和其他TLR2/4配体（包括脂多糖）引发的TLR2/4信号传导。在急性肺损伤模型中，应用GBS透明质酸酶或HA二糖可减轻肺部病理变化和促炎细胞因子水平。我们得出结论，宿主产生的促炎性HA片段分解为二糖使细菌病原体能够逃避免疫检测，并且可作为治疗炎症性疾病的一种策略加以利用。
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