Pyogenic bacterial infections in humans with MyD88 deficiency.
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.
von Bernuth
Horst
H
Human Genetics of Infectious Diseases, INSERM U550, Paris, France.
Picard
Capucine
C
Jin
Zhongbo
Z
Pankla
Rungnapa
R
Xiao
Hui
H
Ku
Cheng-Lung
CL
Chrabieh
Maya
M
Mustapha
Imen Ben
IB
Ghandil
Pegah
P
Camcioglu
Yildiz
Y
Vasconcelos
Júlia
J
Sirvent
Nicolas
N
Guedes
Margarida
M
Vitor
Artur Bonito
AB
Herrero-Mata
María José
MJ
Aróstegui
Juan Ignacio
JI
Rodrigo
Carlos
C
Alsina
Laia
L
Ruiz-Ortiz
Estibaliz
E
Juan
Manel
M
Fortuny
Claudia
C
Yagüe
Jordi
J
Antón
Jordi
J
Pascal
Mariona
M
Chang
Huey-Hsuan
HH
Janniere
Lucile
L
Rose
Yoann
Y
Garty
Ben-Zion
BZ
Chapel
Helen
H
Issekutz
Andrew
A
Maródi
László
L
Rodriguez-Gallego
Carlos
C
Banchereau
Jacques
J
Abel
Laurent
L
Li
Xiaoxia
X
Chaussabel
Damien
D
Puel
Anne
A
Casanova
Jean-Laurent
JL
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
D016207:Cytokines; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors