Highly differentiated human airway epithelial cells: a model to study host cell-parasite interactions in pertussis.
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.
a Division of Pediatric Infectious Diseases , Vanderbilt University School of Medicine.
Claudia
C
Guevara
a Division of Pediatric Infectious Diseases , Vanderbilt University School of Medicine.
Chengxian
C
Zhang
b Tennessee Valley Healthcare Systems , Department of Veterans Affairs.|c Division of Infectious Diseases , Vanderbilt University School of Medicine , Nashville , TN.
Jennifer A
JA
Gaddy
a Division of Pediatric Infectious Diseases , Vanderbilt University School of Medicine.
Junaid
J
Iqbal
a Division of Pediatric Infectious Diseases , Vanderbilt University School of Medicine.
Julio
J
Guerra
d Department of Pediatrics , University of Pittsburgh School of Medicine , Pittsburgh , PA.|e Scientific and Medical Affairs , Sanofi Pasteur , Swiftwater , PA.
David P
DP
Greenberg
e Scientific and Medical Affairs , Sanofi Pasteur , Swiftwater , PA.|f Department of Health Policy , Vanderbilt University School of Medicine , Nashville , TN.
Michael D
MD
Decker
g Department of Biological and Biomedical Sciences, Department of Microbiology and Immunology , University of Maryland School of Medicine , Baltimore , MD.
Nicholas
N
Carbonetti
h Stead Family Department of Pediatrics , University of Iowa Carver College of Medicine , Iowa City , IA.
Timothy D
TD
Starner
h Stead Family Department of Pediatrics , University of Iowa Carver College of Medicine , Iowa City , IA.
Paul B
PB
McCray
i National Institute for Public Health and the Environment, Center for Infectious Diseases Control , Bilthoven , The Netherlands.
Frits R
FR
Mooi
a Division of Pediatric Infectious Diseases , Vanderbilt University School of Medicine.
Oscar G
OG
Gómez-Duarte
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D001422:Bacterial Adhesion / Q000235:genetics; D001886:Bordetella pertussis / Q000235:genetics / Q000502:physiology*; D001980:Bronchi / Q000382:microbiology; D004847:Epithelial Cells / Q000382:microbiology*; D036781:Fimbriae Proteins / Q000235:genetics; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008954:Models, Biological; D061251:Primary Cell Culture; D020545:Respiratory Mucosa / Q000382:microbiology*; D010566:Virulence Factors, Bordetella / Q000235:genetics; D014917:Whooping Cough / Q000382:microbiology*
D000942:Antigens, Bacterial; D010566:Virulence Factors, Bordetella; C101541:fim2 protein, Bordetella; C101542:fim3 protein, Bordetella; C489284:fimD protein, Bordetella; D036781:Fimbriae Proteins
Bordetella pertussis; adherence; fimbriae major subunit Fim2 or Fim3; minor subunit FimD