1. Pyogenic bacterial infections in humans with MyD88 deficiency
- Author
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Andrew C. Issekutz, Manel Juan, Damien Chaussabel, Huey Hsuan Chang, Pegah Ghandil, Laurent Abel, László Maródi, Jean-Laurent Casanova, Capucine Picard, Laia Alsina, Carlos Rodríguez-Gallego, Xiaoxia Li, Lucile Janniere, Horst von Bernuth, Imen Ben Mustapha, Margarida Guedes, Helen Chapel, Claudia Fortuny, Júlia Vasconcelos, Zhongbo Jin, Yoann Rose, Artur Bonito Vitor, Carlos Rodrigo, Anne Puel, Yildiz Camcioglu, Estibaliz Ruiz-Ortiz, Maya Chrabieh, Juan I. Aróstegui, Jacques Banchereau, Ben Zion Garty, Jordi Anton, Jordi Yagüe, Hui Xiao, Cheng-Lung Ku, María José Herrero-Mata, Nicolas Sirvent, Rungnapa Pankla, Mariona Pascal, Génétique Humaine des Maladies Infectieuses (Inserm U980), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), INSERM, U550, Paris, Centre d'étude des Déficits Immunitaires, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Baylor University, Baylor Institute for Immunology Research (BIIR), Khon Kaen University [Thailand], Cleveland Clinic Foundation, Cleveland Clinic, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), Cerrahpasa Medical School, Université d' Istanbul, General Hospital of Santo António, Univ Hosp Archet 2, University Hospital Archet 2, LIRAD–Banco de Sangre y Tejidos, Instituto de Investigación Germans Trias i Pujol, Immunology Department, Hospital Clinic (IDIBAPS), Germans Trias i Pujol Hospital, Barcelona Autonomous University, Hospital Universitari Sant Joan de Deu, University of Barcelona, Inst Invest Germans Trias & Pujol, LIRAD Banco Sangre & Tejidos, IDIBAPS, Dept Immunol, Hosp Clin, University of Oxford [Oxford], Dalhousie University [Halifax], University of Debrecen, Hospital Universitario de Gran Canaria Dr Negrin, Service d'immuno-hématologie pédiatrique [CHU Necker], This work was supported by grants from the INSERM, Agence Nationale de la Recherche, Institut des Maladies Rares, Programme Hospitalier de Recherche Clinique, Banque nationale de Paris Paribas Foundation, and the Dana Foundation (to J.-L.C.), grants from the NIH (U19 AIO57234-02) and the Dana Foundation (to D.C.), grants from the Hungarian Research Fund (to L.M.), and grants FIS/PI060241 (to J.Y.) and FIS/PI070329 (to M.J.)from Spain ’s Ministry of Health. H.v.B. was supported by the Deutsche Forschungsgemeinschaft, Legs Poix, and University San Rafaele Salute. J.-L.C. is an International Scholar of the Howard Hughes Medical Institute. The authors declare that they have no financial conflict of interest. The microarray data used in this study have been deposited in NCBI ’s Gene Expression Omnibus (GEO) with the accession number GSE 12124, Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Baylor Institute for Immunology Research ( BIIR ), Institut Pasteur de Tunis-Réseau International des Instituts Pasteur ( RIIP ), Hospital Clinic ( IDIBAPS ), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Khon Kaen University [Thailand] (KKU)
- Subjects
MESH: Signal Transduction ,Male ,MESH : Cytokines ,[SDV]Life Sciences [q-bio] ,MESH : Gene Deletion ,MESH : Child, Preschool ,[ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,medicine.disease_cause ,Mice ,0302 clinical medicine ,MESH : Child ,MESH: Child ,MESH : Female ,MESH: Animals ,MESH : Pneumococcal Infections ,MESH: Pneumococcal Infections ,Child ,Cell Line, Transformed ,0303 health sciences ,Toll-like receptor ,MESH: Cytokines ,Multidisciplinary ,Toll-Like Receptors ,MESH: Pseudomonas Infections ,MESH : Cell Line, Transformed ,Bacterial Infections ,Orvostudományok ,MESH : Immunity, Innate ,Staphylococcal Infections ,MESH : Pseudomonas Infections ,IRAK4 ,3. Good health ,MESH : Bacterial Infections ,Pneumococcal infections ,Child, Preschool ,Cytokines ,MESH: Immunity, Innate ,Female ,Disease Susceptibility ,MESH : Transfection ,MESH: Toll-Like Receptors ,MESH: Myeloid Differentiation Factor 88 ,Signal Transduction ,Adolescent ,MESH: Bacterial Infections ,MESH : Male ,MESH: Disease Susceptibility ,MESH: Staphylococcal Infections ,Mutation, Missense ,Biology ,Staphylococcal infections ,MESH: Receptors, Interleukin-1 ,Transfection ,Klinikai orvostudományok ,Article ,Pneumococcal Infections ,MESH : Disease Susceptibility ,03 medical and health sciences ,Immunity ,MESH : Adolescent ,MESH : Mice ,MESH : Receptors, Interleukin-1 ,Streptococcus pneumoniae ,medicine ,Animals ,Humans ,Pseudomonas Infections ,MESH: Cell Line, Transformed ,MESH: Mice ,030304 developmental biology ,MESH : Signal Transduction ,MESH: Adolescent ,MESH : Myeloid Differentiation Factor 88 ,MESH: Mutation, Missense ,Innate immune system ,Interleukin-1 receptor–associated kinase 4 deficiency ,MESH: Humans ,[ SDV ] Life Sciences [q-bio] ,MESH: Transfection ,MESH : Humans ,MESH: Child, Preschool ,Receptors, Interleukin-1 ,medicine.disease ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,MESH: Male ,Immunity, Innate ,MESH: Gene Deletion ,MESH : Toll-Like Receptors ,Immunology ,Myeloid Differentiation Factor 88 ,biology.protein ,MESH : Animals ,MESH : Staphylococcal Infections ,MESH: Female ,MESH : Mutation, Missense ,Gene Deletion ,030215 immunology - Abstract
International audience; MyD88 is a key downstream adapter for most Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). MyD88 deficiency in mice leads to susceptibility to a broad range of pathogens in experimental settings of infection. We describe a distinct situation in a natural setting of human infection. Nine children with autosomal recessive MyD88 deficiency suffered from life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease. However, these patients were otherwise healthy, with normal resistance to other microbes. Their clinical status improved with age, but not due to any cellular leakiness in MyD88 deficiency. The MyD88-dependent TLRs and IL-1Rs are therefore essential for protective immunity to a small number of pyogenic bacteria, but redundant for host defense to most natural infections.
- Published
- 2016
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