Fraga-Silva Thais Fernanda de Campos, Boko Mèdéton Mahoussi Michaël, Martins Núbia Sabrina, Cetlin Andrea Antunes, Russo Momtchilo, Vianna Elcio Oliveira, Bonato Vania Luiza Deperon
Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
Basic and Applied Immunology Program, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
J Allergy Clin Immunol Glob. 2022 Sep 20;2(1):14-22. doi: 10.1016/j.jacig.2022.08.003. eCollection 2023 Feb.
Eosinophilic, noneosinophilic, or mixed granulocytic inflammations are the hallmarks of asthma heterogeneity. Depending on the priming of lung immune and structural cells, subjects with asthma might generate immune responses that are T2-prone or T17-prone immune response. Bacterial infections caused by , , or spp. induce the secretion of IL-17, which in turn recruit neutrophils into the airways. Clinical studies and experimental models of asthma indicated that neutrophil infiltration induces a specific phenotype of asthma, characterized by an impaired response to corticosteroid treatment. The understanding of pathways that regulate the T17-neutrophils axis is critical to delineate and develop host-directed therapies that might control asthma and its exacerbation episodes that course with infectious comorbidities. In this review, we outline clinical and experimental studies on the role of airway epithelial cells, S100A9, and high mobility group box 1, which act in concert with the IL-17-neutrophil axis activated by bacterial infections, and are related with asthma that is difficult to treat. Furthermore, we report critically our view in the light of these findings in an attempt to stimulate further investigations and development of immunotherapies for the control of severe asthma.
嗜酸性、非嗜酸性或混合性粒细胞炎症是哮喘异质性的标志。根据肺免疫细胞和结构细胞的预激活情况，哮喘患者可能产生倾向于2型免疫反应或倾向于17型免疫反应的免疫应答。由肺炎链球菌、金黄色葡萄球菌或铜绿假单胞菌引起的细菌感染会诱导白细胞介素-17的分泌，进而将中性粒细胞募集到气道中。哮喘的临床研究和实验模型表明，中性粒细胞浸润会诱发一种特定的哮喘表型，其特征是对皮质类固醇治疗反应受损。了解调节17型免疫反应-中性粒细胞轴的途径对于确定和开发可能控制哮喘及其伴有感染性合并症的加重发作的宿主导向疗法至关重要。在这篇综述中，我们概述了关于气道上皮细胞、S100A9和高迁移率族蛋白B1作用的临床和实验研究，它们与细菌感染激活的17型免疫反应-中性粒细胞轴协同作用，并与难治性哮喘相关。此外，我们根据这些发现批判性地阐述了我们的观点，试图激发对控制重度哮喘的免疫疗法的进一步研究和开发。
