TREM1 regulates antifungal immune responses in invasive pulmonary aspergillosis
Pattern recognition receptors (PRRs) are responsible for Aspergillus fumigatus recognition by innate immunity and its subsequent immune signaling. The triggering receptor expressed on myeloid cells 1 (TREM1) is a recently characterized pro-inflammatory receptor constitutively expressed on the surfac...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-12-01
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| Series: | Virulence |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21505594.2021.1879471 |
| _version_ | 1818976070261538816 |
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| author | L Bernal-Martínez SM Gonçalves B de Andres C Cunha I Gonzalez Jimenez K Lagrou E Mellado ML Gaspar JA Maertens A Carvalho L Alcazar-Fuoli |
| author_facet | L Bernal-Martínez SM Gonçalves B de Andres C Cunha I Gonzalez Jimenez K Lagrou E Mellado ML Gaspar JA Maertens A Carvalho L Alcazar-Fuoli |
| author_sort | L Bernal-Martínez |
| collection | DOAJ |
| description | Pattern recognition receptors (PRRs) are responsible for Aspergillus fumigatus recognition by innate immunity and its subsequent immune signaling. The triggering receptor expressed on myeloid cells 1 (TREM1) is a recently characterized pro-inflammatory receptor constitutively expressed on the surface of neutrophils and macrophages. A soluble form (sTREM1) of this protein that can be detected in human body fluids has been identified. Here we investigated the role of TREM1 during invasive pulmonary aspergillosis (IPA). IPA patients displayed significantly higher levels of sTREM1 in bronchoalveolar lavages when compared to control patients. Functional analysis in TREM1 showed that the levels of sTREM1 and TREM1 pathway-related cytokines were influenced by single nucleotide polymorphisms in TREM1. In addition, we confirmed a role of TREM1 on antifungal host defense against A. fumigatus in a murine model of IPA. TREM1 deficiency increased susceptibility to infection in the immunosuppressed murine host. Deletion of TREM1 showed delayed innate and adaptive immune responses and impaired pro-inflammatory cytokine responses. The absence of TREM1 in primary macrophages attenuated the TLR signaling by altering the expression of both receptor and effector proteins that are critical to the response against A. fumigatus. In this study, and for the first time, we demonstrate the key role for the TREM1 receptor pathway during IPA. |
| first_indexed | 2024-12-20T16:06:00Z |
| format | Article |
| id | doaj.art-4d1d6092559d4913990ac809ed9d0c4b |
| institution | Directory Open Access Journal |
| issn | 2150-5594 2150-5608 |
| language | English |
| last_indexed | 2024-12-20T16:06:00Z |
| publishDate | 2021-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj.art-4d1d6092559d4913990ac809ed9d0c4b2022-12-21T19:34:09ZengTaylor & Francis GroupVirulence2150-55942150-56082021-12-0112157058310.1080/21505594.2021.18794711879471TREM1 regulates antifungal immune responses in invasive pulmonary aspergillosisL Bernal-Martínez0SM Gonçalves1B de Andres2C Cunha3I Gonzalez Jimenez4K Lagrou5E Mellado6ML Gaspar7JA Maertens8A Carvalho9L Alcazar-Fuoli10Mycology Reference Laboratory, National Centre for Microbiology, Instituto De Salud Carlos IIILife and Health Sciences Research Institute (ICVS), School of Medicine, University of MinhoNational Centre for Microbiology, Instituto De Salud Carlos IIILife and Health Sciences Research Institute (ICVS), School of Medicine, University of MinhoMycology Reference Laboratory, National Centre for Microbiology, Instituto De Salud Carlos IIIImmunology, and Transplantation, Laboratory of Clinical Bacteriology and MycologyMycology Reference Laboratory, National Centre for Microbiology, Instituto De Salud Carlos IIINational Centre for Microbiology, Instituto De Salud Carlos IIIImmunology, and Transplantation, Laboratory of Clinical Bacteriology and MycologyLife and Health Sciences Research Institute (ICVS), School of Medicine, University of MinhoMycology Reference Laboratory, National Centre for Microbiology, Instituto De Salud Carlos IIIPattern recognition receptors (PRRs) are responsible for Aspergillus fumigatus recognition by innate immunity and its subsequent immune signaling. The triggering receptor expressed on myeloid cells 1 (TREM1) is a recently characterized pro-inflammatory receptor constitutively expressed on the surface of neutrophils and macrophages. A soluble form (sTREM1) of this protein that can be detected in human body fluids has been identified. Here we investigated the role of TREM1 during invasive pulmonary aspergillosis (IPA). IPA patients displayed significantly higher levels of sTREM1 in bronchoalveolar lavages when compared to control patients. Functional analysis in TREM1 showed that the levels of sTREM1 and TREM1 pathway-related cytokines were influenced by single nucleotide polymorphisms in TREM1. In addition, we confirmed a role of TREM1 on antifungal host defense against A. fumigatus in a murine model of IPA. TREM1 deficiency increased susceptibility to infection in the immunosuppressed murine host. Deletion of TREM1 showed delayed innate and adaptive immune responses and impaired pro-inflammatory cytokine responses. The absence of TREM1 in primary macrophages attenuated the TLR signaling by altering the expression of both receptor and effector proteins that are critical to the response against A. fumigatus. In this study, and for the first time, we demonstrate the key role for the TREM1 receptor pathway during IPA.http://dx.doi.org/10.1080/21505594.2021.1879471trem1aspergillus fumigatusdiagnostic biomarkers and fungal immune response |
| spellingShingle | L Bernal-Martínez SM Gonçalves B de Andres C Cunha I Gonzalez Jimenez K Lagrou E Mellado ML Gaspar JA Maertens A Carvalho L Alcazar-Fuoli TREM1 regulates antifungal immune responses in invasive pulmonary aspergillosis Virulence trem1 aspergillus fumigatus diagnostic biomarkers and fungal immune response |
| title | TREM1 regulates antifungal immune responses in invasive pulmonary aspergillosis |
| title_full | TREM1 regulates antifungal immune responses in invasive pulmonary aspergillosis |
| title_fullStr | TREM1 regulates antifungal immune responses in invasive pulmonary aspergillosis |
| title_full_unstemmed | TREM1 regulates antifungal immune responses in invasive pulmonary aspergillosis |
| title_short | TREM1 regulates antifungal immune responses in invasive pulmonary aspergillosis |
| title_sort | trem1 regulates antifungal immune responses in invasive pulmonary aspergillosis |
| topic | trem1 aspergillus fumigatus diagnostic biomarkers and fungal immune response |
| url | http://dx.doi.org/10.1080/21505594.2021.1879471 |
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