Source: School of Life Sciences
Written by: School of Life Sciences
Edited by: Wang Dongmei

Virus infection in the respiratory tract is the most frequent cause of upper/lower airway inflammation and exacerbation. The airway epithelium lines in the first layer of the mucosa and maintains mucosal homeostasis. NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome is one of the most important intracellular pattern recognition receptors and senses both exogenous and endogenous “danger signals”, leading to the activation of the host innate immune response; while excess activation of the NLRP3 inflammasome also can cause or aggravate the chronic airway mucosal inflammation. Previous studies have only focused on NLRP3 functions in immune cells, but there has been limited information about the functions and roles of inflammasome in airway epithelium. Airway epithelial cell is the main host cell and primary target of various respiratory viruses; and the virus induced cellular alterations including the innate immune response, cell death, cell functional changes will cause the pathological changes in the airway mucosa. Therefore, whether the epithelial NLRP3 inflammasome could orchestrate the virus (e.g., human rhinovirus) induced cellular functional changes and lead to virus-induced disease exacerbation is required to further investigation.

Recently, Prof. Jun Cui’s group from the School of Life Sciences and Prof. Chunwei Li’s group from the First Affiliated Hospital, Sun Yat-sen University, published a research article titled “NLRP3 contributes to inflammation, pyroptosis, and mucin production in human airway epithelium upon rhinovirus infection” in the official journal of the American Academy of Allergy, Asthma & Immunology – Journal of Allergy and Clinical Immunology. The article reveals that the epithelial NLRP3 inflammasome cac mediate IL-1 secretion, pyroptotic cell death, and mucin production upon human rhinovirus infection, in which the above cellular immune and functional changes are the essential mechanisms underlying rhinovirus induced airway remodeling. Dr. Tao Liu graduated from the School of Life Sciences, Yutao Zhou (PhD student), Liqiu Wang (PhD student) from the School of Life Sciences, and Liyue Li (PhD student) from the First Affiliated Hospital are the co-first authors. Prof. Jun Cui and Prof. Chunwei Li are the co-corresponding authors. This study is funded by the National Natural Science Foundation of China.

This study facilitated the human primary nasal epithelial cell culture system which can mimic the functions and characteristics of the human airway epithelium, and demonstrated that human rhinovirus induced cellular immune (IL-1 secretion) and functional changes (pyroptosis and mucin production) were dependent on DDX33/DDX58 – NLRP3 – Caspase-1 – GSDMD signaling axis. This report further found that the epithelium from patients with rhinovirus infection was associated with epithelial mucus hyperproduction, while NLRP3 and IL-1 expression levels were significantly elevated in the rhinovirus infected epithelium with goblet cell hyperplasia compared with normal epithelium.
The current study uncovers the critical role of NLRP3 inflammasome in rhinovirus induced airway epithelial cell immune and functional changes, indicating a novel mechanism in epithelial inflammasome regulating mucosa (host) – pathogen interaction. The results also support that modulation of the NLRP3 inflammasome could a new therapeutic approach to control the rhinovirus induced exacerbation of chronic airway inflammation.

Link: DOI: https://doi.org/10.1016/j.jaci.2019.05.006