Nejvíce citovaný článek - PubMed ID 37307651
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 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 localized predominantly 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 transepithelial electrical resistance (TEER) and staining of the tight junction protein zonula occludens 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 results suggest that the mucus may serve as a niche that allows B. pertussis B1917 to minimize epithelial recognition and damage. The lack of a robust immune response further indicates that additional components of the nasal mucosa, such as innate immune cells, are likely required to initiate an effective host defense.IMPORTANCEThe nasal epithelium is the initial site where Bordetella pertussis comes into contact with the host during respiratory tract infection. In this study, human nasal epithelial cells cultured at the air-liquid interface were established as an in vitro model to investigate the early stages of B. pertussis infection. We showed that the clinical isolate B. pertussis B1917 resides in the mucus during the early stages of colonization without disrupting the epithelial barrier function. Infection results in moderate transcriptomic and proteomic changes, characterized by increased mucus production and minimal inflammatory signaling. These results suggest that B. pertussis B1917 may evade early host recognition by residing in mucus and avoiding direct interaction with epithelial cells. They also highlight the importance of other components of the mucosal immune system, such as resident immune cells, for the initiation of an effective defense.
- Klíčová slova
- Bordetella pertussis, BteA effector, air-liquid interface culture, airway epithelium, human nasal epithelial cell, type III secretion system,
- MeSH
- bakteriální proteiny metabolismus genetika MeSH
- Bordetella pertussis * patogenita genetika fyziologie MeSH
- epitelové buňky * mikrobiologie imunologie metabolismus MeSH
- faktory virulence rodu Bordetella metabolismus MeSH
- hlen mikrobiologie metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- mucin 5AC metabolismus genetika MeSH
- nosní sliznice * mikrobiologie cytologie imunologie MeSH
- pertuse * mikrobiologie imunologie MeSH
- proteomika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- bakteriální proteiny MeSH
- faktory virulence rodu Bordetella MeSH
- mucin 5AC MeSH
Pertussis, or whooping cough, is a highly contagious and acute respiratory illness caused primarily by the gram-negative coccobacillus Bordetella pertussis. Despite near-universal vaccination, pertussis remains one of the least-controlled vaccine-preventable infectious diseases. Since 2023, pertussis incidence has been rising, and widespread pertussis outbreaks have resurged in many countries. In response to these emerging challenges, almost 300 experts from institutions across 24 countries convened at the 14th International Bordetella Symposium in Prague, Czech Republic, from 24 to 28 June 2024 to discuss pertussis epidemiology and research and strategies to mitigate the global pertussis burden. We present here the highlights of the symposium, comprising epidemiological and clinical aspects of Bordetella infections, results of clinical trials of pertussis vaccination in pregnant women and effectiveness of maternal vaccination in protecting newborn infants in Africa and Europe, the controlled human infection model (CHIM), and the latest insights into the biology, immunology, and pathogenesis of B. pertussis infection.
- Klíčová slova
- Bordetella pertussis, epidemiology, pathogenesis, toxins, vaccines, virulence,
- MeSH
- Bordetella pertussis * imunologie MeSH
- celosvětové zdraví MeSH
- kongresy jako téma MeSH
- lidé MeSH
- novorozenec MeSH
- pertuse * prevence a kontrola epidemiologie mikrobiologie MeSH
- pertusová vakcína aplikace a dávkování imunologie MeSH
- těhotenství MeSH
- vakcinace MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kongresy MeSH
- přehledy MeSH
- Názvy látek
- pertusová vakcína MeSH