Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Responds to Virus-Infected Cells with a Significant Increase in Type IV Pilus Expression

ABSTRACT Nontypeable Haemophilus influenzae (NTHI) colonizes the human nasopharynx, but when the host immune response is dysregulated by upper respiratory tract (URT) virus infection, NTHI can gain access to more distal airway sites and cause disease. The NTHI type IV pilus (T4P) facilitates adheren...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Elaine M. Mokrzan, Kolapo A. Dairo, Laura A. Novotny, Lauren O. Bakaletz
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	COPD PilA vaccine adenovirus otitis media respiratory syncytial virus Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e4acfb9464504da5bc4f035404f9393e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e4acfb9464504da5bc4f035404f9393e
record_format	dspace
spelling	oai:doaj.org-article:e4acfb9464504da5bc4f035404f9393e2021-11-15T15:30:16ZNontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Responds to Virus-Infected Cells with a Significant Increase in Type IV Pilus Expression10.1128/mSphere.00384-202379-5042https://doaj.org/article/e4acfb9464504da5bc4f035404f9393e2020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00384-20https://doaj.org/toc/2379-5042ABSTRACT Nontypeable Haemophilus influenzae (NTHI) colonizes the human nasopharynx, but when the host immune response is dysregulated by upper respiratory tract (URT) virus infection, NTHI can gain access to more distal airway sites and cause disease. The NTHI type IV pilus (T4P) facilitates adherence, benign colonization, and infection, and its majority subunit PilA is in clinical trials as a vaccinogen. To further validate the strategy of immunization with PilA against multiple NTHI-induced diseases, it is important to demonstrate T4P expression under microenvironmental conditions that predispose to NTHI infection of the airway. Because URT infection commonly facilitates NTHI-induced diseases, we examined the influence of ongoing virus infection of respiratory tract epithelial cells on NTHI T4P expression in vitro. Polarized primary human airway epithelial cells (HAEs) were sequentially inoculated with one of three common URT viruses, followed by NTHI. Use of a reporter construct revealed that NTHI upregulated pilA promoter activity when cultured with HAEs infected with adenovirus (AV), respiratory syncytial virus (RSV), or rhinovirus (RV) versus that in mock-infected HAEs. Consistent with these results, pilA expression and relative PilA/pilin abundance, as assessed by quantitative reverse transcription-PCR (qRT-PCR) and immunoblot, respectively, were also significantly increased when NTHI was cultured with virus-infected HAEs. Collectively, our data strongly suggest that under conditions of URT virus infection, PilA vaccinogen induction of T4P-directed antibodies is likely to be highly effective against multiple NTHI-induced diseases by interfering with T4P-mediated adherence. We hypothesize that this outcome could thereby limit or prevent the increased load of NTHI in the nasopharynx that characteristically precedes these coinfections. IMPORTANCE Nontypeable Haemophilus influenzae (NTHI) is the predominant bacterial causative agent of many chronic and recurrent diseases of the upper and lower respiratory tracts. NTHI-induced chronic rhinosinusitis, otitis media, and exacerbations of cystic fibrosis and chronic obstructive pulmonary disease often develop during or just after an upper respiratory tract viral infection. We have developed a vaccine candidate immunogen for NTHI-induced diseases that targets the majority subunit (PilA) of the type IV twitching pilus (T4P), which NTHI uses to adhere to respiratory tract epithelial cells and that also plays a role in disease. Here, we showed that NTHI cocultured with virus-infected respiratory tract epithelial cells express significantly more of the vaccine-targeted T4P than NTHI that encounters mock-infected (healthy) cells. These results strongly suggest that a vaccine strategy that targets the NTHI T4P will be effective under the most common predisposing condition: when the human host has a respiratory tract virus infection.Elaine M. MokrzanKolapo A. DairoLaura A. NovotnyLauren O. BakaletzAmerican Society for MicrobiologyarticleCOPDPilAvaccineadenovirusotitis mediarespiratory syncytial virusMicrobiologyQR1-502ENmSphere, Vol 5, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	COPD PilA vaccine adenovirus otitis media respiratory syncytial virus Microbiology QR1-502
spellingShingle	COPD PilA vaccine adenovirus otitis media respiratory syncytial virus Microbiology QR1-502 Elaine M. Mokrzan Kolapo A. Dairo Laura A. Novotny Lauren O. Bakaletz Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Responds to Virus-Infected Cells with a Significant Increase in Type IV Pilus Expression
description	ABSTRACT Nontypeable Haemophilus influenzae (NTHI) colonizes the human nasopharynx, but when the host immune response is dysregulated by upper respiratory tract (URT) virus infection, NTHI can gain access to more distal airway sites and cause disease. The NTHI type IV pilus (T4P) facilitates adherence, benign colonization, and infection, and its majority subunit PilA is in clinical trials as a vaccinogen. To further validate the strategy of immunization with PilA against multiple NTHI-induced diseases, it is important to demonstrate T4P expression under microenvironmental conditions that predispose to NTHI infection of the airway. Because URT infection commonly facilitates NTHI-induced diseases, we examined the influence of ongoing virus infection of respiratory tract epithelial cells on NTHI T4P expression in vitro. Polarized primary human airway epithelial cells (HAEs) were sequentially inoculated with one of three common URT viruses, followed by NTHI. Use of a reporter construct revealed that NTHI upregulated pilA promoter activity when cultured with HAEs infected with adenovirus (AV), respiratory syncytial virus (RSV), or rhinovirus (RV) versus that in mock-infected HAEs. Consistent with these results, pilA expression and relative PilA/pilin abundance, as assessed by quantitative reverse transcription-PCR (qRT-PCR) and immunoblot, respectively, were also significantly increased when NTHI was cultured with virus-infected HAEs. Collectively, our data strongly suggest that under conditions of URT virus infection, PilA vaccinogen induction of T4P-directed antibodies is likely to be highly effective against multiple NTHI-induced diseases by interfering with T4P-mediated adherence. We hypothesize that this outcome could thereby limit or prevent the increased load of NTHI in the nasopharynx that characteristically precedes these coinfections. IMPORTANCE Nontypeable Haemophilus influenzae (NTHI) is the predominant bacterial causative agent of many chronic and recurrent diseases of the upper and lower respiratory tracts. NTHI-induced chronic rhinosinusitis, otitis media, and exacerbations of cystic fibrosis and chronic obstructive pulmonary disease often develop during or just after an upper respiratory tract viral infection. We have developed a vaccine candidate immunogen for NTHI-induced diseases that targets the majority subunit (PilA) of the type IV twitching pilus (T4P), which NTHI uses to adhere to respiratory tract epithelial cells and that also plays a role in disease. Here, we showed that NTHI cocultured with virus-infected respiratory tract epithelial cells express significantly more of the vaccine-targeted T4P than NTHI that encounters mock-infected (healthy) cells. These results strongly suggest that a vaccine strategy that targets the NTHI T4P will be effective under the most common predisposing condition: when the human host has a respiratory tract virus infection.
format	article
author	Elaine M. Mokrzan Kolapo A. Dairo Laura A. Novotny Lauren O. Bakaletz
author_facet	Elaine M. Mokrzan Kolapo A. Dairo Laura A. Novotny Lauren O. Bakaletz
author_sort	Elaine M. Mokrzan
title	Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Responds to Virus-Infected Cells with a Significant Increase in Type IV Pilus Expression
title_short	Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Responds to Virus-Infected Cells with a Significant Increase in Type IV Pilus Expression
title_full	Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Responds to Virus-Infected Cells with a Significant Increase in Type IV Pilus Expression
title_fullStr	Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Responds to Virus-Infected Cells with a Significant Increase in Type IV Pilus Expression
title_full_unstemmed	Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Responds to Virus-Infected Cells with a Significant Increase in Type IV Pilus Expression
title_sort	nontypeable <named-content content-type="genus-species">haemophilus influenzae</named-content> responds to virus-infected cells with a significant increase in type iv pilus expression
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/e4acfb9464504da5bc4f035404f9393e
work_keys_str_mv	AT elainemmokrzan nontypeablenamedcontentcontenttypegenusspecieshaemophilusinfluenzaenamedcontentrespondstovirusinfectedcellswithasignificantincreaseintypeivpilusexpression AT kolapoadairo nontypeablenamedcontentcontenttypegenusspecieshaemophilusinfluenzaenamedcontentrespondstovirusinfectedcellswithasignificantincreaseintypeivpilusexpression AT lauraanovotny nontypeablenamedcontentcontenttypegenusspecieshaemophilusinfluenzaenamedcontentrespondstovirusinfectedcellswithasignificantincreaseintypeivpilusexpression AT laurenobakaletz nontypeablenamedcontentcontenttypegenusspecieshaemophilusinfluenzaenamedcontentrespondstovirusinfectedcellswithasignificantincreaseintypeivpilusexpression
_version_	1718427920885612544

Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Responds to Virus-Infected Cells with a Significant Increase in Type IV Pilus Expression

Ejemplares similares