title: Pyogenic bacterial infections in humans with MyD88 deficiency.
abstract: 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.
authors.affiliation: Human Genetics of Infectious Diseases, INSERM U550, Paris, France.
authors.forename: Horst
authors.initials: H
authors.lastname: von Bernuth
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Zhongbo
authors.initials: Z
authors.lastname: Jin
authors.forename: Rungnapa
authors.initials: R
authors.lastname: Pankla
authors.forename: Hui
authors.initials: H
authors.lastname: Xiao
authors.forename: Cheng-Lung
authors.initials: CL
authors.lastname: Ku
authors.forename: Maya
authors.initials: M
authors.lastname: Chrabieh
authors.forename: Imen Ben
authors.initials: IB
authors.lastname: Mustapha
authors.forename: Pegah
authors.initials: P
authors.lastname: Ghandil
authors.forename: Yildiz
authors.initials: Y
authors.lastname: Camcioglu
authors.forename: Júlia
authors.initials: J
authors.lastname: Vasconcelos
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sirvent
authors.forename: Margarida
authors.initials: M
authors.lastname: Guedes
authors.forename: Artur Bonito
authors.initials: AB
authors.lastname: Vitor
authors.forename: María José
authors.initials: MJ
authors.lastname: Herrero-Mata
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Aróstegui
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodrigo
authors.forename: Laia
authors.initials: L
authors.lastname: Alsina
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Ruiz-Ortiz
authors.forename: Manel
authors.initials: M
authors.lastname: Juan
authors.forename: Claudia
authors.initials: C
authors.lastname: Fortuny
authors.forename: Jordi
authors.initials: J
authors.lastname: Yagüe
authors.forename: Jordi
authors.initials: J
authors.lastname: Antón
authors.forename: Mariona
authors.initials: M
authors.lastname: Pascal
authors.forename: Huey-Hsuan
authors.initials: HH
authors.lastname: Chang
authors.forename: Lucile
authors.initials: L
authors.lastname: Janniere
authors.forename: Yoann
authors.initials: Y
authors.lastname: Rose
authors.forename: Ben-Zion
authors.initials: BZ
authors.lastname: Garty
authors.forename: Helen
authors.initials: H
authors.lastname: Chapel
authors.forename: Andrew
authors.initials: A
authors.lastname: Issekutz
authors.forename: László
authors.initials: L
authors.lastname: Maródi
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodriguez-Gallego
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.forename: Damien
authors.initials: D
authors.lastname: Chaussabel
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D000293:Adolescent; D000818:Animals; D001424:Bacterial Infections / Q000235:genetics* / Q000276:immunology*; D002461:Cell Line, Transformed; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D004198:Disease Susceptibility; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D020125:Mutation, Missense; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D011008:Pneumococcal Infections / Q000235:genetics / Q000276:immunology; D011552:Pseudomonas Infections / Q000235:genetics / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D014162:Transfection
chemical_list: D016207:Cytokines; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors