Intercellular adhesion molecule 1 serves as a primary cognate receptor for the Type IV pilus of nontypeableHaemophilus influenzae
- 26 February 2016
- journal article
- Published by Hindawi Limited in Cellular Microbiology
- Vol. 18 (8), 1043-1055
- https://doi.org/10.1111/cmi.12575
Abstract
Nontypeable Haemophilus influenzae (NTHI) utilizes the Type IV pilus (Tfp) to adhere to respiratory tract epithelial cells thus colonizing its human host; however, the host cell receptor to which this adhesive protein binds is unknown. From a panel of receptors engaged by Tfp expressed by other bacterial species, we showed that the majority subunit of NTHI Tfp, PilA, bound to intercellular adhesion molecule 1 (ICAM1) and that this interaction was both specific and of high affinity. Further, Tfp-expressing NTHI inoculated on to polarized respiratory tract epithelial cells that expressed ICAM1 were significantly more adherent compared to Tfp-deficient NTHI or NTHI inoculated on to epithelial cells to which ICAM1 gene expression was silenced. Moreover, pre-incubation of epithelial cells with recombinant soluble PilA (rsPilA) blocked adherence of NTHI, an outcome that was abrogated by admixing rsPilA with ICAM1 prior to application on to the target cells. Epithelial cells infected with adenovirus or respiratory syncytial virus showed increased expression of ICAM1; this outcome supported augmented adherence of Tfp-expressing NTHI. Collectively, these data revealed the cognate receptor for NTHI Tfp as ICAM1 and promote continued development of a Tfp-targeted vaccine for NTHI-induced diseases of the airway wherein upper respiratory tract viruses play a key predisposing role.Keywords
Funding Information
- NIDCD/NIH (R01 003915)
This publication has 48 references indexed in Scilit:
- Viral and Bacterial Interactions in the Upper Respiratory TractPLoS Pathogens, 2013
- Haemophilus influenzae Protein F Mediates Binding to Laminin and Human Pulmonary Epithelial CellsThe Journal of Infectious Diseases, 2012
- Biological Roles of Nontypeable Haemophilus influenzae Type IV Pilus Proteins Encoded by the pil and com OperonsJournal of Bacteriology, 2012
- Transcutaneous immunization as preventative and therapeutic regimens to protect against experimental otitis media due to nontypeable Haemophilus influenzaeMucosal Immunology, 2011
- Characterization of a Mutant Escherichia coli Heat-Labile Toxin, LT(R192G/L211A), as a Safe and Effective Oral AdjuvantClinical and Vaccine Immunology, 2011
- Epitope mapping immunodominant regions of the PilA protein of nontypeable Haemophilus influenzae (NTHI) to facilitate the design of two novel chimeric vaccine candidatesVaccine, 2009
- A Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Homologue Plays a Pivotal Role in Nontypeable Haemophilus influenzae Colonization of the Chinchilla Nasopharynx via the Outer Membrane Protein P5-Homologous AdhesinInfection and Immunity, 2008
- Genomic Sequence of an Otitis Media Isolate of Nontypeable Haemophilus influenzae : Comparative Study with H. influenzae Serotype d, Strain KW20Journal of Bacteriology, 2005
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Blocking Intercellular Adhesion Molecule-1 on Human Epithelial Cells Decreases Respiratory Syncytial Virus InfectionBiochemical and Biophysical Research Communications, 2001