Dectin-1 Is Expressed in Human Lung and Mediates the Proinflammatory Immune Response to Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>

ABSTRACT The C-type lectin receptor Dectin-1 is expressed mainly on myeloid cells mediating the immune response targeting respiratory pathogens such as Aspergillus fumigatus and Mycobacterium tuberculosis. The pulmonary epithelium serves as an important interface for interactions between these patho...

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Autores principales:	Kerstin A. Heyl, Tilman E. Klassert, Annina Heinrich, Mario M. Müller, Esther Klaile, Hendrik Dienemann, Christiane Grünewald, Robert Bals, Bernhard B. Singer, Hortense Slevogt
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5cf63d7ba7944300976d3bccc0b5b65f
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spelling	oai:doaj.org-article:5cf63d7ba7944300976d3bccc0b5b65f2021-11-15T15:45:55ZDectin-1 Is Expressed in Human Lung and Mediates the Proinflammatory Immune Response to Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>10.1128/mBio.01492-142150-7511https://doaj.org/article/5cf63d7ba7944300976d3bccc0b5b65f2014-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01492-14https://doaj.org/toc/2150-7511ABSTRACT The C-type lectin receptor Dectin-1 is expressed mainly on myeloid cells mediating the immune response targeting respiratory pathogens such as Aspergillus fumigatus and Mycobacterium tuberculosis. The pulmonary epithelium serves as an important interface for interactions between these pathogens and the respiratory tract. Therefore, we analyzed the expression pattern of Dectin-1 in the human lung. Immunohistochemically stained human lung sections from 17 out of 19 individuals were positive for Dectin-1, which was expressed mainly apically on bronchial and alveolar epithelium. Our results showed no correlation with chronic obstructive pulmonary disease (COPD) or the smoking habits of the patients. Nontypeable Haemophilus influenzae (NTHI), an important bacterial pathogen of the respiratory tract with significant importance in COPD, has also been proposed to be recognized by Dectin-1, suggesting a possible impact on the NTHI-dependent immune response in human airways. Therefore, the involvement of Dectin-1 in NTHI-triggered cytokine responses was investigated in primary normal human bronchial epithelial (NHBE) cells and in the A549 cell line stably transfected with Dectin-1. The presence of Dectin-1 significantly increased cytokine release in response to NTHI in NHBE and A549 cells. In addition, phosphorylation of the Dectin-1 hem-immunoreceptor tyrosine-based activation motif (hemITAM) was essential for the Dectin-1-triggered response to NTHI in A549 cells. In conclusion, in human airways, epithelium-expressed Dectin-1 may play a significant role in generating an NTHI-mediated, proinflammatory immune response. IMPORTANCE In this study, we demonstrated, for the first time, the expression of Dectin-1 on human lung tissues and, in particular, pulmonary epithelium by making use of immunohistochemical staining. The epithelial lining of the human airways is an important interface for host-pathogen interactions. Therefore, our data suggest that epithelium-expressed Dectin-1 is of considerable importance for the interaction of the human airways with pathogens detected by this receptor, such as A. fumigatus and M. tuberculosis. Moreover, we further demonstrated that, in pulmonary epithelial cells, Dectin-1 enhances the proinflammatory immune response to NTHI. In COPD patients, NTHI is a major cause of respiratory tract infections and is associated with proinflammatory immune responses in the lower airways. Therefore, our data suggest that the functional interaction of Dectin-1 with NTHI in human airways may have an important impact on the pathogenesis of COPD.Kerstin A. HeylTilman E. KlassertAnnina HeinrichMario M. MüllerEsther KlaileHendrik DienemannChristiane GrünewaldRobert BalsBernhard B. SingerHortense SlevogtAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 5 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Kerstin A. Heyl Tilman E. Klassert Annina Heinrich Mario M. Müller Esther Klaile Hendrik Dienemann Christiane Grünewald Robert Bals Bernhard B. Singer Hortense Slevogt Dectin-1 Is Expressed in Human Lung and Mediates the Proinflammatory Immune Response to Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>
description	ABSTRACT The C-type lectin receptor Dectin-1 is expressed mainly on myeloid cells mediating the immune response targeting respiratory pathogens such as Aspergillus fumigatus and Mycobacterium tuberculosis. The pulmonary epithelium serves as an important interface for interactions between these pathogens and the respiratory tract. Therefore, we analyzed the expression pattern of Dectin-1 in the human lung. Immunohistochemically stained human lung sections from 17 out of 19 individuals were positive for Dectin-1, which was expressed mainly apically on bronchial and alveolar epithelium. Our results showed no correlation with chronic obstructive pulmonary disease (COPD) or the smoking habits of the patients. Nontypeable Haemophilus influenzae (NTHI), an important bacterial pathogen of the respiratory tract with significant importance in COPD, has also been proposed to be recognized by Dectin-1, suggesting a possible impact on the NTHI-dependent immune response in human airways. Therefore, the involvement of Dectin-1 in NTHI-triggered cytokine responses was investigated in primary normal human bronchial epithelial (NHBE) cells and in the A549 cell line stably transfected with Dectin-1. The presence of Dectin-1 significantly increased cytokine release in response to NTHI in NHBE and A549 cells. In addition, phosphorylation of the Dectin-1 hem-immunoreceptor tyrosine-based activation motif (hemITAM) was essential for the Dectin-1-triggered response to NTHI in A549 cells. In conclusion, in human airways, epithelium-expressed Dectin-1 may play a significant role in generating an NTHI-mediated, proinflammatory immune response. IMPORTANCE In this study, we demonstrated, for the first time, the expression of Dectin-1 on human lung tissues and, in particular, pulmonary epithelium by making use of immunohistochemical staining. The epithelial lining of the human airways is an important interface for host-pathogen interactions. Therefore, our data suggest that epithelium-expressed Dectin-1 is of considerable importance for the interaction of the human airways with pathogens detected by this receptor, such as A. fumigatus and M. tuberculosis. Moreover, we further demonstrated that, in pulmonary epithelial cells, Dectin-1 enhances the proinflammatory immune response to NTHI. In COPD patients, NTHI is a major cause of respiratory tract infections and is associated with proinflammatory immune responses in the lower airways. Therefore, our data suggest that the functional interaction of Dectin-1 with NTHI in human airways may have an important impact on the pathogenesis of COPD.
format	article
author	Kerstin A. Heyl Tilman E. Klassert Annina Heinrich Mario M. Müller Esther Klaile Hendrik Dienemann Christiane Grünewald Robert Bals Bernhard B. Singer Hortense Slevogt
author_facet	Kerstin A. Heyl Tilman E. Klassert Annina Heinrich Mario M. Müller Esther Klaile Hendrik Dienemann Christiane Grünewald Robert Bals Bernhard B. Singer Hortense Slevogt
author_sort	Kerstin A. Heyl
title	Dectin-1 Is Expressed in Human Lung and Mediates the Proinflammatory Immune Response to Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>
title_short	Dectin-1 Is Expressed in Human Lung and Mediates the Proinflammatory Immune Response to Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>
title_full	Dectin-1 Is Expressed in Human Lung and Mediates the Proinflammatory Immune Response to Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>
title_fullStr	Dectin-1 Is Expressed in Human Lung and Mediates the Proinflammatory Immune Response to Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>
title_full_unstemmed	Dectin-1 Is Expressed in Human Lung and Mediates the Proinflammatory Immune Response to Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>
title_sort	dectin-1 is expressed in human lung and mediates the proinflammatory immune response to nontypeable <named-content content-type="genus-species">haemophilus influenzae</named-content>
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/5cf63d7ba7944300976d3bccc0b5b65f
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Dectin-1 Is Expressed in Human Lung and Mediates the Proinflammatory Immune Response to Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content>

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