Respiratory viral infection increases host susceptibility to secondary bacterial infections, yet the precise dynamics within airway epithelia remain elusive. Here, we elucidate the pivotal role of CD47 in the airway epithelium during bacterial super-infection. We demonstrated that upon influenza virus infection, CD47 expression was upregulated and localized on the apical surface of ciliated cells within primary human nasal or bronchial epithelial cells. This induced CD47 exposure provided attachment sites for Staphylococcus aureus, thereby compromising the epithelial barrier integrity. Through bacterial adhesion assays and in vitro pull-down assays, we identified fibronectin-binding proteins (FnBP) of S. aureus as a key component that binds to CD47. Furthermore, we found that ciliated cell-specific CD47 deficiency or neutralizing antibody-mediated CD47 inactivation enhanced in vivo survival rates. These findings suggest that interfering with the interaction between airway epithelial CD47 and pathogenic bacterial FnBP holds promise for alleviating the adverse effects of super-infection.

Background: As treatment responses differ according to the inflammatory endotype of chronic rhinosinusitis (CRS), identifying the endotype could facilitate personalized treatment. We aimed to identify a noninvasive epithelial lining fluid (ELF) biomarker for the type 2 (T2) endotype of CRS.Methods: Nasal tissue and ELF samples were obtained from patients with CRS and control individuals. Single‐cell RNA sequencing (scRNA‐seq) data were analyzed. The expression of inflammatory mediators was measured using Luminex multiplex assays and enzyme‐linked immunosorbent assays.Results: Analysis of the scRNA‐seq data revealed that CST1 was exclusively expressed in epithelial cells of T2 CRS, but not in those of non‐T2 CRS, and this was confirmed by immunofluorescence staining. Cystatin SN expression was detected in ELF, and its levels were significantly higher in T2 CRS than in non‐T2 CRS and controls. The expression level of cystatin SN in the ELF was positively correlated with the Lund‐Mackay CT, SNOT‐22, and JESREC scores, whereas it was inversely correlated with olfactory function. Furthermore, ELF cystatin SN levels correlated with the tissue/blood eosinophil count and nasal tissue expression of T2 inflammatory mediators, indicating that ELF cystatin SN is a reliable marker of nasal T2 inflammation. In the receiver operating characteristics curve analysis evaluating the predictive efficacy for T2 CRS, the AUC for ELF cystatin SN was 0.894 (0.936 in the validation cohort), which was higher than that of other markers, including blood eosinophil count, serum total IgE level, and the JESREC score. With a cut‐off value of 112.5 ng/mg, ELF cystatin SN yielded a 75.0% sensitivity and 92.0% specificity.Conclusions: ELF cystatin SN is a clinically feasible, noninvasive biomarker with superior accuracy for predicting T2 CRS.

Recent advancements in medical management, endoscopic sinus surgery, and biologics have significantly improved outcomes for patients with chronic rhinosinusitis (CRS). However, long-term recurrence is frequently observed following endoscopic sinus surgery, with symptoms worsening after biologics are discontinued. Consequently, refractory or recurrent CRS remains a significant challenge, causing a substantial healthcare burden. In this review, we provide current insights into mucosal inflammatory memory, a potential mechanism leading to CRS recurrence. Given that both immune and non-immune cells in the sinonasal mucosa play critical roles in the pathophysiology of CRS, a deeper understanding of the mechanisms underlying mucosal inflammatory memory in various cellular components of sinonasal tissue could aid in the management of refractory CRS. We describe and discuss the latest knowledge regarding the novel concept of inflammatory memory, including both adaptive immune memory and trained immunity. Additionally, we summarize the pathogenic memory features of the sinonasal mucosa cellular components in the context of CRS.

Moon S, et al. Allergy Asthma Immunol Res. 2024 Nov;16(6):585-600. https://doi.org/10.4168/aair.2024.16.6.585

Han S, et al. Immune Netw. 2023 Oct;23(5):e42. https://doi.org/10.4110/in.2023.23.e42