Pyogenic bacterial infections in humans with MyD88 deficiency.

Horst von Bernuth (1, 2) , Capucine Picard (1, 3, 2) , Zhongbo Jin (4, 5) , Rungnapa Pankla (6, 5) , Hui Xiao (7) , L. Ku (1, 2) , Maya Chrabieh (1, 2) , Imen Ben Mustapha (1, 2, 8) , Pegah Ghandil (1, 2) , Yildiz Camcioglu (9) , Júlia Vasconcelos (10) , Nicolas Sirvent (11, 12) , Margarida Guedes (10) , Artur Bonito Vitor (13) , J. Herrero-Mata (13) , J. Arostegui (14) , Carlos Rodrigo (15) , Laia Alsina (16) , Estibaliz Ruiz-Ortiz (17) , Manel Juan (14) , Claudia Fortuny , J. Yague (14) , J. Anton , Mariona Pascal (18) , Huey-Hsuan Chang , Lucile Janniere (1, 2) , Yoann Rose (1, 2) , Ben-Zion Garty , Helen Chapel (19) , Andrew Issekutz (20) , L. Marodi (21) , Carlos Rodriguez-Gallego (22) , Jacques Banchereau (5) , Laurent Abel (1, 2) , Xiaoxia Li (8) , Damien Chaussabel (5) , Anne Puel (1, 2) , Jean-Laurent Casanova (23, 1, 2)

1 Inserm U980 - Génétique Humaine des Maladies Infectieuses
2 INSERM, U550, Paris
3 Centre d'étude des Déficits Immunitaires
4 Baylor University
5 BIIR - Baylor Institute for Immunology Research
6 KKU - Khon Kaen University [Thailand]
7 Cleveland Clinic Foundation
8 Institut Pasteur de Tunis
9 Cerrahpasa Medical School
10 General Hospital of Santo António
11 Univ Hosp Archet 2
12 University Hospital Archet 2
13 LIRAD–Banco de Sangre y Tejidos
14 Immunology Department
15 Germans Trias i Pujol Hospital
16 Hospital Universitari Sant Joan de Deu, University of Barcelona
17 Inst Invest Germans Trias & Pujol, LIRAD Banco Sangre & Tejidos
18 IDIBAPS, Dept Immunol, Hosp Clin
19 University of Oxford
20 Dalhousie University [Halifax]
21 University of Debrecen Egyetem [Debrecen]
22 Hospital Universitario de Gran Canaria Dr Negrin
23 Service d'immuno-hématologie pédiatrique [CHU Necker]

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.

Domaines: Sciences du Vivant [q-bio]; Bactériologie

Horst von Bernuth, Capucine Picard, Zhongbo Jin, Rungnapa Pankla, Hui Xiao, et al.. Pyogenic bacterial infections in humans with MyD88 deficiency.. Science, 2008, 321 (5889), pp.691-6. ⟨10.1126/science.1158298⟩. ⟨pasteur-01375224⟩