Population variation in NAIP functional copy number confers increased cell death upon Legionella pneumophila infection

Autor: Brigitte Gicquel, Ludovic Tailleux, Lluis Quintana-Murci, Carmen Buchrieser, Sylvie Garcia, Michele Boniotto, Mariella Lomma
Přispěvatelé: Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génétique mycobactérienne - Mycobacterial genetics, Institut Pasteur [Paris], Biologie des bactéries intracellulaires, Biologie des Populations Lymphocytaires, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], M.L. was holder of a Marie Curie fellowship financed by the European Commission (INTRAPATH Project MEST-CT-2005-020715) coordinated by Institut Pasteur and received support from the Fondation pour la Recherche Médicale. This work was supported by the Institut Pasteur, the ANR (ANR-08-MIEN-009-01), the Fondation pour la Recherche Médicale (FRM), the CNRS, and an EPFL-Debiopharm Life Sciences award to L. Q.-M., ANR-08-MIEN-0009,EVOLSENSORS,Génomique évolutive des senseurs de l'immunité innée: les familles NLR, RLR et CLR de type-2 chez l'homme(2008), European Project: 35418,INTRAPATH, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)
Jazyk: angličtina
Rok vydání: 2012
Předmět:
MESH: Cell Death
Asia
DNA Copy Number Variations
Immunology
Black People
Legionella
MESH: Legionnaires' Disease
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
MESH: Protein Isoforms
Legionella pneumophila
Microbiology
03 medical and health sciences
0302 clinical medicine
Gene Duplication
NAIP
Gene duplication
MESH: Up-Regulation
Humans
Protein Isoforms
Immunology and Allergy
Copy-number variation
Gene
030304 developmental biology
Genomic organization
Genetics
0303 health sciences
Innate immune system
MESH: Humans
Cell Death
biology
MESH: Neuronal Apoptosis-Inhibitory Protein
Copy number variation
MESH: Asia
MESH: Gene Duplication
General Medicine
biology.organism_classification
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Neuronal Apoptosis-Inhibitory Protein
Up-Regulation
Europe
biology.protein
MESH: DNA Copy Number Variations
MESH: African Continental Ancestry Group
MESH: Europe
Legionnaires' Disease
Infection
Flagellin
030215 immunology
Zdroj: Human Immunology
Human Immunology, Elsevier, 2012, 73 (2), pp.196-200. ⟨10.1016/j.humimm.2011.10.014⟩
Human Immunology, 2012, 73 (2), pp.196-200. ⟨10.1016/j.humimm.2011.10.014⟩
ISSN: 0198-8859
Popis: International audience; The NAIP gene encodes an intracellular innate immunity receptor that senses flagellin. The genomic region containing NAIP presents a complex genomic organization and includes various NAIP paralogs. Here, we assessed the degree of copy number variation of the complete NAIP gene (NAIPFull) in various human populations and studied the functional impact of such variation on host cell fate using Legionella pneumophila as an infection model. We determined that African populations have a NAIPFull duplication at a higher frequency than Europeans and Asians, with an increased transcription of the gene. In addition, we demonstrated that a higher amount of the NAIPFull protein dramatically increases cell death upon infection by L. pneumophila, a mechanism that may account for increased host resistance to infection. We postulate that the NAIPFull gene duplication might have been evolutionary maintained, or even selected for, because it may confer an advantage to the host against flagellated bacteria.
Databáze: OpenAIRE
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