TREM1 regulates antifungal immune responses in invasive pulmonary aspergillosis

Autor: Samuel M. Gonçalves, B de Andres, María Luisa Gaspar, Leticia Bernal-Martinez, Agostinho Carvalho, J Maertens, Emilia Mellado, Laura Alcazar-Fuoli, Cristina Cunha, Katrien Lagrou, I Gonzalez Jimenez
Přispěvatelé: Fundação para a Ciência e a Tecnologia (Portugal), Horizon 2020, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Fundación La Caixa, Unión Europea. Comisión Europea. H2020, Fundação para a Ciência e Tecnologia (Portugal)
Rok vydání: 2021
Předmět:
Male
animal diseases
Infectious and parasitic diseases
RC109-216
Aspergillus fumigatus
Mice
TREM1
skin and connective tissue diseases
Receptor
Lung
Invasive Pulmonary Aspergillosis
0303 health sciences
biology
aspergillus fumigatus
Pattern recognition receptor
Middle Aged
diagnostic biomarkers and fungal immune response
3. Good health
Infectious Diseases
Cytokines
Female
Bronchoalveolar Lavage Fluid
Research Article
Research Paper
Adult
Microbiology (medical)
Antifungal
Immune signaling
medicine.drug_class
Immunology
chemical and pharmacologic phenomena
Microbiology
Immunocompromised Host
03 medical and health sciences
Immune system
medicine
Animals
Humans
030304 developmental biology
Innate immune system
030306 microbiology
biochemical phenomena
metabolism
and nutrition
Invasive pulmonary aspergillosis
biology.organism_classification
Immunity
Innate
Triggering Receptor Expressed on Myeloid Cells-1
Disease Models
Animal
Gene Expression Regulation
bacteria
Parasitology
Zdroj: Repisalud
Instituto de Salud Carlos III (ISCIII)
Virulence
article-version (VoR) Version of Record
Virulence, Vol 12, Iss 1, Pp 570-583 (2021)
ISSN: 2150-5608
2150-5594
Popis: 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. This work was supported by the Fundação para a Ciência e a Tecnologia [PTDC/SAU-SER/29635/2017]; Fundação para a Ciência e a Tecnologia [UIDB/50026/2020 and UIDP/50026/2020]; Fundação para a Ciência e a Tecnologia [PTDC/MED-GEN/28778/2017]; H2020 Excellent Science [NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023)]; Instituto de Salud Carlos III [RD16/CIII/0004/0003]; Instituto de Salud Carlos III [PI18CIII/00045]; Instituto de Salud Carlos III [MPY 1277/15]; Ministerio de Ciencia, Innovación y Universidades [RTI2018-099114-B-I00]; Associação Viver a Ciência (PT) [SFRH/BD/136814/2018]; “la Caixa” Foundation [ID 100010434]. Sí
Databáze: OpenAIRE
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