Limited response of primary nasal epithelial cells to Bordetella pertussis infection and the effector protein BteA

Abstract

Bordetella pertussis is a Gram-negative coccobacillus that causes whooping cough or pertussis, a respiratory disease that has recently experienced a resurgence. Upon entering the respiratory tract, B. pertussis colonizes the airway epithelium and attaches to ciliated cells. Here, we used primary human nasal epithelial cells (hNECs) cultured at the air-liquid interface, and investigated their interaction with the B. pertussis B1917, focusing on the role of the type III secretion system effector protein BteA. In this model, which resembles the epithelial cells of nasal epithelium in vivo, B. pertussis B1917 initially replicated in the overlying mucus and scarcely colonized the cell cilia. The colonization led to a gradual decline in epithelial barrier function, as shown by measurements of trans-epithelial electrical resistance (TEER) and staining of the tight junction protein zonula occludens 1 (ZO-1). The decrease in TEER occurred independently of the cytotoxic effector protein BteA. Transcriptomic and proteomic analyses of hNECs showed only moderate changes following infection, primarily characterized by increased mucus production, including upregulation of mucin MUC5AC. No profound response to BteA was detected. Furthermore, the infection did not induce production of inflammatory cytokines, suggesting that B. pertussis B1917 evades recognition by hNECs in this model system. These findings suggest that the bacterium may utilize the mucus layer in the airways as a protective niche to minimize epithelial recognition and damage. ImportanceThe nasal epithelium is the initial site where B. pertussis comes into contact with the host during respiratory infection. This work established human nasal epithelial cells (hNECs) cultured at the air-liquid interface (ALI) as an in vitro model to investigate B. pertussis infection. Using this system, we were able to show that in the early stages of colonization the clinical isolate B. pertussis B1917 replicates in the mucus without disrupting epithelial barrier function. Infection results in moderate transcriptomic and proteomic changes and is characterized by increased mucus production and minimal inflammatory signaling.