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Use of the EpiAirway Model for Characterizing Long-term Host-pathogen Interactions
Published on: September 2, 2011
Highly differentiated human airway epithelial cells: a model to study host cell-parasite interactions in pertussis
Claudia Guevara1, Chengxian Zhang1, Jennifer A Gaddy2,3
1a Division of Pediatric Infectious Diseases , Vanderbilt University School of Medicine.
Background:
Bordetella pertussis colonizes the human respiratory mucosa. Most studies on B. pertussis adherence have relied on cultured mammalian cells that lack key features present in differentiated human airway cells or on animal models that are not natural hosts of B. pertussis. The objectives of this work were to evaluate B. pertussis infection in highly differentiated human airway cells in vitro and to show the role of B. pertussis fimbriae in cell adherence.
Methods:
Primary human airway epithelial (PHAE) cells from human bronchi and a human bronchial epithelial (HBE) cell line were grown in vitro under air-liquid interface conditions.
Results:
PHAE and HBE cells infected with B. pertussis wild-type strain revealed bacterial adherence to the apical surface of cells, bacteria-induced cytoskeleton changes, and cell detachment. Mutations in the major fimbrial subunits Fim2/3 or in the minor fimbrial adhesin subunit FimD affected B. pertussis adherence to predominantly HBE cells. This cell model recapitulates the morphologic features of the human airway infected by B. pertussis and confirms the role of fimbriae in B. pertussis adherence. Furthermore, HBE cells show that fimbrial subunits, and specifically FimD adhesin, are critical in B. pertussis adherence to airway cells.
Conclusions:
The relevance of this model to study host-parasite interaction in pertussis lies in the striking physiologic and morphologic similarity between the PHAE and HBE cells and the human airway ciliated and goblet cells in vivo. These cells can proliferate in vitro, differentiate, and express the same genetic profile as human respiratory cells in vivo.
Insights
Bordetella pertussis adheres to human airway cells, with fimbriae playing a key role. This study uses a novel cell model to investigate pertussis infection and bacterial adherence mechanisms.
Area of Science:
- Microbiology
- Cell Biology
- Infectious Diseases
Background:
- Bordetella pertussis colonizes human respiratory tracts.
- Previous studies on B. pertussis adherence used less relevant cell or animal models.
- Lack of suitable in vitro models hinders understanding of B. pertussis infection.
Purpose of the Study:
- To evaluate B. pertussis infection in highly differentiated human airway cells in vitro.
- To investigate the role of B. pertussis fimbriae in bacterial adherence to airway cells.
Main Methods:
- Primary human airway epithelial (PHAE) cells and a human bronchial epithelial (HBE) cell line were cultured under air-liquid interface conditions.
- B. pertussis wild-type and mutant strains were used to infect the differentiated airway cell models.
- Bacterial adherence, cytoskeleton changes, and cell morphology were analyzed.
Main Results:
- B. pertussis adhered to the apical surface of PHAE and HBE cells, causing cytoskeleton alterations and cell detachment.
- Mutations in fimbrial subunits (Fim2/3) or adhesin (FimD) significantly reduced B. pertussis adherence, particularly in HBE cells.
- The study confirmed the critical role of fimbriae, especially FimD, in B. pertussis adherence to airway epithelial cells.
Conclusions:
- The PHAE and HBE cell models accurately recapitulate the in vivo human airway environment for studying B. pertussis infection.
- These differentiated cell models are physiologically and morphologically similar to human ciliated and goblet cells.
- The findings highlight the importance of fimbriae and FimD in B. pertussis host-parasite interactions.
