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Science 1 August 2008:
Vol. 321. no. 5889, pp. 691 - 696
DOI: 10.1126/science.1158298
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Reports

Pyogenic Bacterial Infections in Humans with MyD88 Deficiency

Horst von Bernuth,1,2 Capucine Picard,1,2,3 Zhongbo Jin,4,5 Rungnapa Pankla,4,6 Hui Xiao,7 Cheng-Lung 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 Margarida Guedes,10 Artur Bonito Vitor,12 María José Herrero-Mata,13 Juan Ignacio Aróstegui,14 Carlos Rodrigo,15 Laia Alsina,16 Estibaliz Ruiz-Ortiz,13 Manel Juan,14 Claudia Fortuny,16 Jordi Yagüe,14 Jordi Antón,16 Mariona Pascal,14 Huey-Hsuan Chang,17 Lucile Janniere,1,2 Yoann Rose,1,2 Ben-Zion Garty,18 Helen Chapel,19 Andrew Issekutz,20 László Maródi,21 Carlos Rodriguez-Gallego,22 Jacques Banchereau,4 Laurent Abel,1,2 Xiaoxia Li,7 Damien Chaussabel,4 Anne Puel,1,2 Jean-Laurent Casanova1,2,23*

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.

1 Human Genetics of Infectious Diseases, INSERM U550, Paris, France.
2 Paris Descartes University, France.
3 Study Center of Primary Immunodeficiencies, Assistance Publique Hôpitaux de Paris, Necker Hospital, Paris, France.
4 Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
5 Baylor University, Waco, TX 76798, USA.
6 Khon Kaen University, Thailand.
7 Cleveland Clinic Foundation, OH 44195, USA.
8 Pasteur Institute of Tunis, Tunisia.
9 Cerrahpasa Medical School, Istanbul University, Turkey.
10 General Hospital of Santo António, Porto, Portugal.
11 University Hospital Archet 2, Nice, France.
12 Hospital S.João, Porto, Portugal.
13 LIRAD–Banco de Sangre y Tejidos, Instituto de Investigación Germans Trias i Pujol, Badalona, Barcelona, Spain.
14 Immunology Department, Hospital Clinic, IDIBAPS, Barcelona, Spain.
15 Germans Trias i Pujol Hospital, Barcelona Autonomous University, Spain.
16 Sant Joan de Déu Hospital, Barcelona University, Spain.
17 Dendritic Cell Immunobiology, Institut Pasteur and INSERM U818, Paris, France.
18 Schneider Children's Medical Center, Petah Tiqva, Israel.
19 University of Oxford and Oxford Radcliffe Hospital, Oxford, UK.
20 Dalhousie University, Halifax, Nova Scotia, Canada.
21 Debrecen University, Hungary.
22 Gran Canaria Dr Negrin Hospital, Las Palmas de Gran Canaria, Spain.
23 Pediatric Hematology-Immunology Unit, Necker Hospital, Paris, France.

* To whom correspondence should be addressed. E-mail: jean-laurent.casanova{at}inserm.fr

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