PDF(Pubmed)
Abstract：
Streptococcus pneumoniae (Sp) frequently causes secondary pneumonia after influenza A virus (IAV) infection, leading to high morbidity and mortality worldwide. Concomitant pneumococcal and influenza vaccination improves protection against coinfection but does not always yield complete protection. Impaired innate and adaptive immune responses have been associated with attenuated bacterial clearance in influenza virus-infected hosts. In this study, we showed that preceding low-dose IAV infection caused persistent Sp infection and suppression of bacteria-specific T-helper type 17 (Th17) responses in mice. Prior Sp infection protected against subsequent IAV/Sp coinfection by improving bacterial clearance and rescuing bacteria-specific Th17 responses in the lungs. Furthermore, blockade of IL-17A by anti-IL-17A antibodies abrogated the protective effect of Sp preinfection. Importantly, memory Th17 responses induced by Sp preinfection overcame viral-driven Th17 inhibition and provided cross-protection against different Sp serotypes following coinfection with IAV. These results indicate that bacteria-specific Th17 memory cells play a key role in providing protection against IAV/Sp coinfection in a serotype-independent manner and suggest that a Th17-based vaccine would have excellent potential to mitigate disease caused by coinfection. IMPORTANCE Streptococcus pneumoniae (Sp) frequently causes secondary bacterial pneumonia after influenza A virus (IAV) infection, leading to increased morbidity and mortality worldwide. Current pneumococcal vaccines induce highly strain-specific antibody responses and provide limited protection against IAV/Sp coinfection. Th17 responses are broadly protective against Sp single infection, but whether the Th17 response, which is dramatically impaired by IAV infection in naïve mice, might be effective in immunization-induced protection against pneumonia caused by coinfection is not known. In this study, we have revealed that Sp-specific memory Th17 cells rescue IAV-driven inhibition and provide cross-protection against subsequent lethal coinfection with IAV and different Sp serotypes. These results indicate that a Th17-based vaccine would have excellent potential to mitigate disease caused by IAV/Sp coinfection.
摘要：
肺炎链球菌(Sp)常引起甲型流感病毒(IAV)感染后继发肺炎,导致世界范围内的高发病率和高死亡率。伴随的肺炎球菌和流感疫苗接种可改善对合并感染的保护，但并不总是产生完全的保护。在流感病毒感染的宿主中,受损的先天和适应性免疫应答与减毒的细菌清除有关。在这项研究中,我们发现,之前的低剂量IAV感染导致小鼠持续的Sp感染和抑制细菌特异性T辅助型17(Th17)应答.先前的Sp感染通过改善细菌清除和挽救肺中细菌特异性Th17反应来保护免受随后的IAV/Sp共感染。此外，抗IL-17A抗体对IL-17A的阻断消除了Sp预感染的保护作用。重要的是,Sp感染前诱导的记忆Th17反应克服了病毒驱动的Th17抑制，并在与IAV共感染后提供了针对不同Sp血清型的交叉保护。这些结果表明,细菌特异性Th17记忆细胞在以血清型非依赖性方式提供针对IAV/Sp共感染的保护中起关键作用,并且表明基于Th17的疫苗将具有减轻由共感染引起的疾病的极好潜力。重要肺炎链球菌（Sp）常引起甲型流感病毒（IAV）感染后继发细菌性肺炎，导致全球发病率和死亡率增加。目前的肺炎球菌疫苗诱导高度菌株特异性的抗体应答,并提供针对IAV/Sp共感染的有限保护。Th17反应对Sp单一感染具有广泛的保护作用，但是Th17的反应，在幼稚小鼠中，IAV感染会严重损害，可能是有效的免疫诱导的保护，以防止由共同感染引起的肺炎是未知的。在这项研究中,我们发现，Sp特异性记忆Th17细胞挽救了IAV驱动的抑制，并提供了针对随后与IAV和不同Sp血清型的致死性共感染的交叉保护。这些结果表明,基于Th17的疫苗将具有减轻由IAV/Sp共感染引起的疾病的极好潜力。
