The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia.

Phagocytosis and inflammation within the lungs is crucial for host defense during bacterial pneumonia. Triggering receptor expressed on myeloid cells (TREM)-2 was proposed to negatively regulate TLR-mediated responses and enhance phagocytosis by macrophages, but the role of TREM-2 in respiratory tra...

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Autores principales:	Omar Sharif, Riem Gawish, Joanna M Warszawska, Rui Martins, Karin Lakovits, Anastasiya Hladik, Bianca Doninger, Julia Brunner, Ana Korosec, Roland E Schwarzenbacher, Tiina Berg, Robert Kralovics, Jacques Colinge, Ildiko Mesteri, Susan Gilfillan, Andrea Salmaggi, Admar Verschoor, Marco Colonna, Sylvia Knapp
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b2865b62e70f463aadd680a610a73fae
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spelling	oai:doaj.org-article:b2865b62e70f463aadd680a610a73fae2021-11-11T06:06:10ZThe triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia.1553-73661553-737410.1371/journal.ppat.1004167https://doaj.org/article/b2865b62e70f463aadd680a610a73fae2014-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24945405/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Phagocytosis and inflammation within the lungs is crucial for host defense during bacterial pneumonia. Triggering receptor expressed on myeloid cells (TREM)-2 was proposed to negatively regulate TLR-mediated responses and enhance phagocytosis by macrophages, but the role of TREM-2 in respiratory tract infections is unknown. Here, we established the presence of TREM-2 on alveolar macrophages (AM) and explored the function of TREM-2 in the innate immune response to pneumococcal infection in vivo. Unexpectedly, we found Trem-2(-/-) AM to display augmented bacterial phagocytosis in vitro and in vivo compared to WT AM. Mechanistically, we detected that in the absence of TREM-2, pulmonary macrophages selectively produced elevated complement component 1q (C1q) levels. We found that these increased C1q levels depended on peroxisome proliferator-activated receptor-δ (PPAR-δ) activity and were responsible for the enhanced phagocytosis of bacteria. Upon infection with S. pneumoniae, Trem-2(-/-) mice exhibited an augmented bacterial clearance from lungs, decreased bacteremia and improved survival compared to their WT counterparts. This work is the first to disclose a role for TREM-2 in clinically relevant respiratory tract infections and demonstrates a previously unknown link between TREM-2 and opsonin production within the lungs.Omar SharifRiem GawishJoanna M WarszawskaRui MartinsKarin LakovitsAnastasiya HladikBianca DoningerJulia BrunnerAna KorosecRoland E SchwarzenbacherTiina BergRobert KralovicsJacques ColingeIldiko MesteriSusan GilfillanAndrea SalmaggiAdmar VerschoorMarco ColonnaSylvia KnappPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 6, p e1004167 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Omar Sharif Riem Gawish Joanna M Warszawska Rui Martins Karin Lakovits Anastasiya Hladik Bianca Doninger Julia Brunner Ana Korosec Roland E Schwarzenbacher Tiina Berg Robert Kralovics Jacques Colinge Ildiko Mesteri Susan Gilfillan Andrea Salmaggi Admar Verschoor Marco Colonna Sylvia Knapp The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia.
description	Phagocytosis and inflammation within the lungs is crucial for host defense during bacterial pneumonia. Triggering receptor expressed on myeloid cells (TREM)-2 was proposed to negatively regulate TLR-mediated responses and enhance phagocytosis by macrophages, but the role of TREM-2 in respiratory tract infections is unknown. Here, we established the presence of TREM-2 on alveolar macrophages (AM) and explored the function of TREM-2 in the innate immune response to pneumococcal infection in vivo. Unexpectedly, we found Trem-2(-/-) AM to display augmented bacterial phagocytosis in vitro and in vivo compared to WT AM. Mechanistically, we detected that in the absence of TREM-2, pulmonary macrophages selectively produced elevated complement component 1q (C1q) levels. We found that these increased C1q levels depended on peroxisome proliferator-activated receptor-δ (PPAR-δ) activity and were responsible for the enhanced phagocytosis of bacteria. Upon infection with S. pneumoniae, Trem-2(-/-) mice exhibited an augmented bacterial clearance from lungs, decreased bacteremia and improved survival compared to their WT counterparts. This work is the first to disclose a role for TREM-2 in clinically relevant respiratory tract infections and demonstrates a previously unknown link between TREM-2 and opsonin production within the lungs.
format	article
author	Omar Sharif Riem Gawish Joanna M Warszawska Rui Martins Karin Lakovits Anastasiya Hladik Bianca Doninger Julia Brunner Ana Korosec Roland E Schwarzenbacher Tiina Berg Robert Kralovics Jacques Colinge Ildiko Mesteri Susan Gilfillan Andrea Salmaggi Admar Verschoor Marco Colonna Sylvia Knapp
author_facet	Omar Sharif Riem Gawish Joanna M Warszawska Rui Martins Karin Lakovits Anastasiya Hladik Bianca Doninger Julia Brunner Ana Korosec Roland E Schwarzenbacher Tiina Berg Robert Kralovics Jacques Colinge Ildiko Mesteri Susan Gilfillan Andrea Salmaggi Admar Verschoor Marco Colonna Sylvia Knapp
author_sort	Omar Sharif
title	The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia.
title_short	The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia.
title_full	The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia.
title_fullStr	The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia.
title_full_unstemmed	The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia.
title_sort	triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/b2865b62e70f463aadd680a610a73fae
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The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia.

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