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首页> 外文期刊>Infection and immunity >Host Genetic Variations and Sex Differences Potentiate Predisposition, Severity, and Outcomes of Group A Streptococcus-Mediated Necrotizing Soft Tissue Infections
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Host Genetic Variations and Sex Differences Potentiate Predisposition, Severity, and Outcomes of Group A Streptococcus-Mediated Necrotizing Soft Tissue Infections

机译：宿主遗传变异和性别差异增强了A群链球菌介导的坏死性软组织感染的易感性，严重性和结果

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Host genetic variations play an important role in several pathogenic diseases, and we previously provided strong evidence that these genetic variations contribute significantly to differences in susceptibility and clinical outcomes of invasive group A Streptococcus (GAS) patients, including sepsis and necrotizing soft tissue infections (NSTIs). The goal of the present study was to investigate how genetic variations and sex differences among four commonly used mouse strains contribute to variation in severity, manifestations, and outcomes of NSTIs. DBA/2J mice were more susceptible to NSTIs than C57BL/6J, BALB/c, and CD-1 mice, as exhibited by significantly greater bacteremia, excessive dissemination to the spleen, and significantly higher mortality. Differences in the sex of the mice also contributed to differences in disease severity and outcomes: DBA/2J female mice were relatively resistant compared to their male counterparts. However, DBA/2J mice exhibited minimal weight loss and developed smaller lesions than did the aforementioned strains. Moreover, at 48 h after infection, compared with C57BL/6J mice, DBA/2J mice had increased bacteremia, excessive dissemination to the spleen, and excessive concentrations of inflammatory cytokines and chemokines. These results indicate that variations in the host genetic context as well as sex play a dominant role in determining the severity of and susceptibility to GAS NSTIs.
机译：宿主遗传变异在几种致病性疾病中起着重要作用，并且我们先前提供了有力的证据，这些遗传变异极大地促进了A组侵袭性链球菌（GAS）患者的敏感性和临床结局差异，包括败血症和坏死性软组织感染（NSTI） ）。本研究的目的是研究四种常用小鼠品系之间的遗传变异和性别差异如何导致NSTI的严重性，表现和结果变异。 DBA / 2J小鼠比C57BL / 6J，BALB / c和CD-1小鼠更易受NSTI感染，这表现为明显更高的菌血症，过度向脾脏扩散和明显更高的死亡率。小鼠性别的差异也导致了疾病严重程度和预后的差异：与雄性雌性小鼠相比，DBA / 2J雌性小鼠具有相对抗性。然而，与上述品系相比，DBA / 2J小鼠表现出最小的体重减轻并产生了较小的损伤。而且，在感染后48小时，与C57BL / 6J小鼠相比，DBA / 2J小鼠的菌血症增加，对脾脏的过度扩散以及炎性细胞因子和趋化因子的浓度过高。这些结果表明，宿主遗传背景以及性别的变异在确定GAS NSTI的严重性和易感性方面起着主导作用。

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