Influenza enhances host susceptibility to non-pulmonary invasive <i>Streptococcus pyogenes</i> infections

<i>Streptococcus pyogenes</i> (group A streptococcus; GAS) causes a variety of invasive diseases (iGAS) such as bacteremia, toxic shock syndrome, and pneumonia, which are associated with high mortality despite the susceptibility of the bacteria to penicillin <i>ex vivo</i>. Epidemiologic studies indicate that respiratory influenza virus infection is associated with an increase in the frequency of iGAS diseases, including those not directly involving the lung. We modified a murine model of influenza A (IAV)-GAS superinfection to determine if viral pneumonia increased the susceptibility of mice subsequently infected with GAS in the peritoneum. The results showed that respiratory IAV infection increased the morbidity (weight loss) of mice infected intraperitoneally (i.p.) with GAS 3, 5, and 10 d after the initial viral infection. Mortality was also significantly increased when mice were infected with GAS 3 and 5 d after pulmonary IAV infection. Increased mortality among mice infected with virus 5 d prior to bacterial infection correlated with increased dissemination of GAS from the peritoneum to the blood, spleen, and lungs. The interval was also associated with a significant increase in the pro-inflammatory cytokines IFN-γ, IL-12, TNF-α, MCP-1 and IL-27 in sera. We conclude, using a murine model, that respiratory influenza virus infection increases the likelihood and severity of systemic iGAS disease, even when GAS infection does not originate in the respiratory tract.

化脓性链球菌（Streptococcus pyogenes）（即A群链球菌，GAS）可引发多种侵袭性疾病（侵袭性A群链球菌感染，iGAS），包括菌血症、中毒性休克综合征及肺炎；尽管该菌在体外对青霉素敏感，但此类疾病的死亡率仍处于较高水平。流行病学研究表明，呼吸道流感病毒感染与侵袭性A群链球菌感染的发病频次升高存在关联，其中亦涵盖未直接累及肺部的病例。我们对甲型流感病毒（IAV）-GAS重叠感染的小鼠模型进行了改良，旨在探究病毒性肺炎是否会提升小鼠后续经腹腔感染GAS的易感性。结果显示，在初次病毒感染后的第3、5及10天，经腹腔（i.p.）感染GAS的小鼠的发病情况（体重下降）均因呼吸道甲型流感病毒感染而加重。当小鼠在呼吸道甲型流感病毒感染后的第3天或第5天感染GAS时，其死亡率亦显著升高。在细菌感染前5天先感染病毒的小鼠中，死亡率升高与GAS从腹腔向血液、脾脏及肺部的播散增强显著相关。该感染间隔时间还与小鼠血清中促炎细胞因子干扰素γ（IFN-γ）、白细胞介素12（IL-12）、肿瘤坏死因子α（TNF-α）、单核细胞趋化蛋白1（MCP-1）及白细胞介素27（IL-27）的水平显著升高相关。本研究通过小鼠模型得出结论：即便GAS感染并非起源于呼吸道，呼吸道流感病毒感染仍会提升全身性侵袭性A群链球菌感染的发生概率与严重程度。

搜集汇总

背景与挑战

背景概述

该数据集基于小鼠模型研究，探讨了呼吸道流感病毒感染如何增加宿主对非肺部侵袭性链球菌感染的易感性和疾病严重性，即使细菌感染不直接涉及肺部。数据集包括实验数据如补充图表，支持流感与链球菌共感染机制的分析，发布于2023年，涉及医学、微生物学和免疫学等领域。