Nontypeable Haemophilus influenzae Type IV Pilus Mediates Augmented Adherence to Rhinovirus-Infected Human Airway Epithelial Cells
| Autor: | Lauren O. Bakaletz, Michelle Ratkiewicz, Stephen L. Toone, Laura A. Novotny, Binh L. Phong |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Rhinovirus 030106 microbiology Immunology Primary Cell Culture Context (language use) Respiratory Mucosa Biology medicine.disease_cause Microbiology Pilus Bacterial Adhesion Haemophilus influenzae 03 medical and health sciences Antigens CD medicine otorhinolaryngologic diseases Humans RNA Messenger Adhesins Bacterial Common cold Epithelial Cells Bacterial Infections medicine.disease Intercellular Adhesion Molecule-1 Antibodies Neutralizing Bacterial adhesin 030104 developmental biology Infectious Diseases medicine.anatomical_structure Gene Expression Regulation Host-Pathogen Interactions biology.protein Parasitology Fimbriae Proteins Antibody Cell Adhesion Molecules Respiratory tract Protein Binding Signal Transduction |
| Zdroj: | Infect Immun |
| ISSN: | 1098-5522 |
| Popis: | Human rhinovirus (hRV) is frequently detected in the upper respiratory tract, and symptomatic infection is associated with an increased nasopharyngeal bacterial load, with subsequent development of secondary bacterial diseases. Nontypeable Haemophilus influenzae (NTHI) is a commensal bacterial species of the human nasopharynx; however, in the context of prior or concurrent upper respiratory tract viral infection, this bacterium commonly causes multiple diseases throughout the upper and lower respiratory tracts. The present study was conducted to determine the mechanism(s) by which hRV infection promotes the development of NTHI-induced diseases. We showed that hRV infection of polarized primary human airway epithelial cells resulted in increased adherence of NTHI, due in part to augmented expression of CEACAM1 and ICAM1, host cell receptors to which NTHI binds via engagement of multiple adhesins. Antibody blockade of these host cell receptors significantly reduced NTHI adherence. With a specific focus on the NTHI type IV pilus (T4P), which we have previously shown binds to ICAM1, an essential adhesin and virulence determinant, we next showed that T4P-directed antibody blockade significantly reduced NTHI adherence to hRV-infected airway cells and, further, that expression of this adhesin was required for the enhanced adherence observed. Collectively, these data provide a mechanism by which "the common cold" promotes diseases due to NTHI, and they add further support for the use of PilA (the majority subunit of T4P) as a vaccine antigen, since antibodies directed against PilA are expected to limit the notably increased bacterial load associated with hRV coinfection and thereby to prevent secondary NTHI-induced diseases of the respiratory tract. |
| Databáze: | OpenAIRE |
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