Cysteinyl leukotriene receptor 1 expression identifies a subset of neutrophils during the antiviral response that contributes to postviral atopic airway disease

Abstract

CD49d and CysLTR1-coexpressing PMNs are present during symptoms of an acute viral respiratory tract infection in human subjects. Further study is needed to examine selective targeting of proatopic neutrophils as a potential therapeutic strategy to prevent development of postviral atopic airway disease.

Respiratory viral infections and atopic development: From possible mechanisms to advances in treatment

“…Interestingly, challenge with an antigen to which the subject was not sensitized did not lead to an increase in this PMN subset [46]. Finally, we recently have shown that human CD49d + PMN (but not CD49d -PMN) from nasal lavage express CysLTR1 [40].…”

“…In order to induce expression of FcεRI on lung cDC, a specific subset of neutrophils (PMN) expressing CD49d needed to be recruited to the airways. These PMN express the receptor for cysteinyl leukotrienes, CysLTR1, and in vitro cysteinyl leukotrienes impair PMN apoptosis [40]. In vivo, blockade of CysLTR1 led to reduced accumulation of CD49d + PMN in the airways (and prevented development of AHR and MCM) [40].…”

“…These PMN express the receptor for cysteinyl leukotrienes, CysLTR1, and in vitro cysteinyl leukotrienes impair PMN apoptosis [40]. In vivo, blockade of CysLTR1 led to reduced accumulation of CD49d + PMN in the airways (and prevented development of AHR and MCM) [40]. CD49d + PMN in the airways then bound to airway cDC through CD11b/CD18 (the binding partner on the cDC remains unknown).…”

Neutrophil Diversity in Health and Disease

“…Other populations of neutrophils identified in inflammatory/infectious conditions include CD63 + [76] or PD-L1 + [77] neutrophils identified in the airways of cystic fibrosis patients; CD64 + neutrophils, that are increased in sepsis or systemic infections (e.g., pneumonia) [78]; neutrophils expressing receptor activator of nuclear factor κΒ ligand (RANKL)a member of the tumor necrosis factor (TNF) superfamilyidentified in the blood of chronic obstructive pulmonary disease patients [79]; CD49d + cysteinyl leukotriene receptor 1 (CysLTR1) + neutrophils present in the nasal lavage fluid of patients with respiratory tract infections caused by different viruses (e.g., influenza virus, respiratory syncytial virus, or rhinovirus) [80]; human leukocyte antigen -DR isotype (HLA-DR) + neutrophils present in Brazilian patients with leishmaniasis [81]; and para-and proinflammatory neutrophil populations that are present in the oral cavity of healthy or chronic periodontal disease subjects, respectively [82,83]. The question remains whether these populations are distinct subsets derived through differentiation or via activation by cytokines present during ongoing disease/inflammatory processes.…”

Asthma and viral infections

“…66e68 Infants hospitalized with RSV and other viruses have robust neutrophil influx in the airway epithelium. 69 We identified a potential pathway for the role of neutrophils in virus-induced disease in a mouse model, where, using Sendai virus (a rodent respiratory virus similar to RSV), we found that the virally infected mice developed postviral atopic disease via recruitment of a subset of neutrophils (CD49d expressing) through production of cysteinyl leukotrienes. These neutrophils then induced expression of the high-affinity IgE receptor (FcƐRI) on lung conventional dendritic cells.…”