Antigen-specific memory Th17 cells promote cross-protection against nontypeable Haemophilus influenzae after mild influenza A virus infection.
Antigen-specific memory Th17 cells promote cross-protection against nontypeable Haemophilus influenzae after mild influenza A virus infection.
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DOI：
10.1016/j.mucimm.2023.01.007
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发表时间：
2023-04
影响因子：
8
通讯作者：
Abt, Michael C.
中科院分区：
文献类型：
--
作者：
Zhang, Xinyun;Yang, Ying;Chen, ShengSen;Li, Wenchao;Li, Yong;Akerley, Brian J.;Shao, Linyun;Zhang, Wenhong;Shen, Hao;Abt, Michael C.
甲型流感病毒(IAV)感染后继发性细菌性肺炎是世界范围内与IAV感染相关的住院和死亡的主要原因。非分型流感嗜血杆菌(NTHi)是继发性细菌性肺炎最常见的原因之一。目前开发针对NTHi感染的疫苗的努力集中在诱导抗体上，但由于NTHi毒株之间的抗原性差异而受阻。因此，我们研究了记忆T辅助细胞17型(Th17)应答在预防IAV/NTHi混合感染的保护性免疫中的作用。我们观察到，与NTHi单一感染的小鼠相比，即使轻微的IAV感染也会损害NTHi特异性的Th17反应，并增加发病率和死亡率。然而，先前NTHi感染诱导的预先存在的记忆NTHi特异性Th17细胞克服了IAV驱动的Th17抑制，并对不同的NTHi毒株具有交叉保护作用。最后，用诱导强烈Th17记忆反应的NTHi蛋白免疫的小鼠，在与联合感染攻击后，对不同的NTHi毒株具有广泛的保护作用。这些结果表明，将IAV感染限制在轻微疾病的疫苗接种可能不足以消除致命的继发性细菌性肺炎的风险。然而，尽管持续存在IAV感染，NTHi特异性记忆Th17细胞仍提供独立于血清型的保护，并展示了开发针对继发性细菌性肺炎的广泛保护性Th17诱导疫苗的优势。
Secondary bacterial pneumonia after influenza A virus (IAV) infection is the leading cause of hospitalization and death associated with IAV infection worldwide. Nontypeable Haemophilus influenzae (NTHi) is one of the most common causes of secondary bacterial pneumonia. Current efforts to develop vaccines against NTHi infection focus on inducing antibodies but are hindered by antigenic diversity among NTHi strains. Therefore, we investigated the contribution of the memory T helper type 17 (Th17) response in protective immunity against IAV/NTHi coinfection. We observed that even a mild IAV infection impaired the NTHi-specific Th17 response and increased morbidity and mortality compared with NTHi monoinfected mice. However, pre-existing memory NTHi-specific Th17 cells induced by a previous NTHi infection overcame IAV-driven Th17 inhibition and were cross-protective against different NTHi strains. Last, mice immunized with a NTHi protein that induced a strong Th17 memory response were broadly protected against diverse NTHi strains after challenge with coinfection. These results indicate that vaccination that limits IAV infection to mild disease may be insufficient to eliminate the risk of a lethal secondary bacterial pneumonia. However, NTHi-specific memory Th17 cells provide serotype-independent protection despite an ongoing IAV infection and demonstrate the advantage of developing broadly protective Th17-inducing vaccines against secondary bacterial pneumonia.
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