Gailleton Romain, Mathew Nimitha R, Reusch Laura, Schön Karin, Scharf Lydia, Strömberg Anneli, Cvjetkovic Andrea, Aziz Luaay, Hellgren Johan, Tang Ka-Wei, Bemark Mats, Angeletti Davide
Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg 413 90, Sweden.
Department of Clinical Immunology and Transfusion Medicine, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg 413 46, Sweden.
Proc Natl Acad Sci U S A. 2025 Mar 25;122(12):e2421724122. doi: 10.1073/pnas.2421724122. Epub 2025 Mar 20.
The nasal mucosa is the first immunologically active site that respiratory viruses encounter and establishing immunity at the initial point of pathogen contact is essential for preventing viral spread. Influenza A virus (IAV) in humans preferentially replicates in the upper respiratory tract (URT) but mouse models of infection result in lower respiratory tract infection. Here, we optimize IAV inoculation to enhance replication in the nasal turbinate (NT) and study local B cell immunity. We demonstrate that URT-targeted IAV infection stimulates robust local B cell responses, including germinal center (GC) B cell formation in the NT, outside of classical nasal-associated lymphoid tissues. NT GC contributes to local tissue-resident B cell generation and enhances local antibody production. Furthermore, URT-focused immunization also induces significant GC formation in the NT. Finally, we detect steady-state GC in the NT of both mice and healthy humans, suggesting continuous immune surveillance triggered by environmental stimuli. These findings highlight the pivotal role of the NT in local and systemic immunity, with important implications for future mucosal vaccines targeting the upper airways.
鼻粘膜是呼吸道病毒遇到的第一个免疫活性部位，在病原体接触的初始点建立免疫对于预防病毒传播至关重要。人类甲型流感病毒（IAV）优先在上呼吸道（URT）复制，但感染的小鼠模型会导致下呼吸道感染。在这里，我们优化IAV接种以增强在鼻甲骨（NT）中的复制，并研究局部B细胞免疫。我们证明，靶向URT的IAV感染会刺激强大的局部B细胞反应，包括在经典鼻相关淋巴组织之外的NT中生发中心（GC）B细胞的形成。NT GC有助于局部组织驻留B细胞的产生并增强局部抗体产生。此外，聚焦URT的免疫接种还会在NT中诱导显著的GC形成。最后，我们在小鼠和健康人类的NT中检测到稳态GC，表明由环境刺激触发的持续免疫监视。这些发现突出了NT在局部和全身免疫中的关键作用，对未来针对上呼吸道的粘膜疫苗具有重要意义。
