Understanding the mechanism of protective immunity in the nasal mucosae is central to the design of more effective vaccines that prevent nasal infection and transmission of Bordetella pertussis. We found significant infiltration of IL-17-secreting CD4⁺ tissue-resident memory T (T_RM) cells and Siglec-F⁺ neutrophils into the nasal tissue during primary infection with B. pertussis. Il17A^−/− mice had significantly higher bacterial load in the nasal mucosae, associated with significantly reduced infiltration of Siglec-F⁺ neutrophils. Re-infected convalescent mice rapidly cleared B. pertussis from the nasal cavity and this was associated with local expansion of IL-17-producing CD4⁺ T_RM cells. Depletion of CD4 T cells from the nasal tissue during primary infection or after re-challenge of convalescent mice significantly delayed clearance of bacteria from the nasal mucosae. Protection was lost in Il17A^−/− mice and this was associated with significantly less infiltration of Siglec-F⁺ neutrophils and antimicrobial peptide (AMP) production. Finally, depletion of neutrophils reduced the clearance of B. pertussis following re-challenge of convalescent mice. Our findings demonstrate that IL-17 plays a critical role in natural and acquired immunity to B. pertussis in the nasal mucosae and this effect is mediated by mobilizing neutrophils, especially Siglec-F⁺ neutrophils, which have high neutrophil extracellular trap (NET) activity.

了解鼻粘膜的保护性免疫机制对于设计更有效的预防百日咳博德特氏菌鼻部感染和传播的疫苗至关重要。我们发现在初次感染百日咳杆菌期间，分泌 IL-17 的 CD4 ⁺组织驻留记忆 T (T _RM ) 细胞和 Siglec-F ⁺中性粒细胞显着浸润到鼻组织中。Il17A ^-/-小鼠鼻粘膜中的细菌负荷显着增加，与显着减少的 Siglec-F ⁺中性粒细胞浸润有关。再次感染的恢复期小鼠迅速清除了百日咳杆菌来自鼻腔，这与产生 IL-17 的 CD4 ⁺ T _RM细胞的局部扩增有关。在初次感染期间或恢复期小鼠再次受到攻击后，鼻组织中 CD4 T 细胞的消耗显着延迟了鼻粘膜细菌的清除。Il17A ^-/-小鼠的保护作用丧失，这与显着减少的 Siglec-F ⁺中性粒细胞浸润和抗菌肽 (AMP) 产生有关。最后，中性粒细胞的耗尽减少了恢复期小鼠再次受到攻击后百日咳杆菌的清除率。我们的研究结果表明，IL-17 在对百日咳杆菌的天然和获得性免疫中起着关键作用在鼻粘膜中，这种作用是通过动员中性粒细胞介导的，尤其是具有高中性粒细胞胞外陷阱 (NET) 活性的 Siglec-F ^{+中性粒细胞。}