Document Detail


Experimental and natural infections in MyD88- and IRAK-4-deficient mice and humans.
MedLine Citation:
PMID:  23255009     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Most Toll-like-receptors (TLRs) and interleukin-1 receptors (IL-1Rs) signal via myeloid differentiation primary response 88 (MyD88) and interleukin-1 receptor-associated kinase 4 (IRAK-4). The combined roles of these two receptor families in the course of experimental infections have been assessed in MyD88- and IRAK-4-deficient mice for almost fifteen years. These animals have been shown to be susceptible to 46 pathogens: 27 bacteria, eight viruses, seven parasites, and four fungi. Humans with inborn MyD88 or IRAK-4 deficiency were first identified in 2003. They suffer from naturally occurring life-threatening infections caused by a small number of bacterial species, although the incidence and severity of these infections decrease with age. Mouse TLR- and IL-1R-dependent immunity mediated by MyD88 and IRAK-4 seems to be vital to combat a wide array of experimentally administered pathogens at most ages. By contrast, human TLR- and IL-1R-dependent immunity mediated by MyD88 and IRAK-4 seems to be effective in the natural setting against only a few bacteria and is most important in infancy and early childhood. The roles of TLRs and IL-1Rs in protective immunity deduced from studies in mutant mice subjected to experimental infections should therefore be reconsidered in the light of findings for natural infections in humans carrying mutations as discussed in this review.
Authors:
Horst von Bernuth; Capucine Picard; Anne Puel; Jean-Laurent Casanova
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  European journal of immunology     Volume:  42     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-20     Completed Date:  2013-02-12     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  3126-35     Citation Subset:  IM    
Copyright Information:
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bacterial Infections / genetics,  immunology*
Disease Models, Animal
Humans
Immunologic Deficiency Syndromes / genetics,  immunology*
Interleukin-1 Receptor-Associated Kinases / genetics,  immunology*
Mice
Mice, Knockout
Myeloid Differentiation Factor 88 / genetics,  immunology*
Receptors, Interleukin-1 / genetics,  immunology
Toll-Like Receptors / genetics,  immunology
Grant Support
ID/Acronym/Agency:
5UL1RR024143-03/RR/NCRR NIH HHS; UL1 RR024143/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/MYD88 protein, human; 0/Myd88 protein, mouse; 0/Myeloid Differentiation Factor 88; 0/Receptors, Interleukin-1; 0/Toll-Like Receptors; EC 2.7.11.1/IRAK4 protein, human; EC 2.7.11.1/Interleukin-1 Receptor-Associated Kinases; EC 2.7.11.1/Irak4 protein, mouse
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