Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Mucosal Immunol. 2021 Sep;14(5):1183-1202. doi: 10.1038/s41385-021-00407-5. Epub 2021 May 11.
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) 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 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.
了解鼻黏膜保护性免疫的机制对于设计更有效的疫苗以预防百日咳博德特氏菌的鼻腔感染和传播至关重要。我们发现，在原发性百日咳博德特氏菌感染期间，IL-17 分泌的 CD4 组织驻留记忆 T（T）细胞和 Siglec-F 中性粒细胞大量浸润到鼻组织中。Il17A 小鼠鼻黏膜中的细菌负荷明显更高，Siglec-F 中性粒细胞浸润明显减少。再感染恢复期小鼠迅速从鼻腔清除百日咳博德特氏菌，这与局部产生 IL-17 的 CD4 T 细胞的扩增有关。在原发性感染或恢复期小鼠再挑战时，从鼻组织中耗尽 CD4 T 细胞会显著延迟鼻黏膜中细菌的清除。在 Il17A 小鼠中失去了保护作用，这与 Siglec-F 中性粒细胞和抗菌肽（AMP）产生的浸润明显减少有关。最后，在恢复期小鼠再挑战时耗尽中性粒细胞会降低百日咳博德特氏菌的清除率。我们的研究结果表明，IL-17 在鼻黏膜中对百日咳博德特氏菌的天然和获得性免疫中起着关键作用，这种作用是通过动员中性粒细胞，特别是具有高中性粒细胞胞外陷阱（NET）活性的 Siglec-F 中性粒细胞来介导的。
