Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor-dependent innate antiviral immune responses.

Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor-dependent innate antiviral immune responses. Research Abstract Details 

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Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor-dependent innate antiviral immune responses. Abstract Text:

Douglas R McDonald,Daniel Brown,Francisco A Bonilla,Raif S Geha,

BACKGROUND: Engagement of all known Toll-like receptors (TLRs) causes the production of inflammatory cytokines, including TNF-alpha, whereas in humans, engagement of TLRs 3, 7, 8, and 9 also induces type I IFNs. IRAK-4 is a critical effector in signaling by TLRs and the IL-1 receptor, which share homology in their intracellular domain and recruit IRAK-4 via the adaptor myeloid differentiation factor 88 (MyD88). Patients with IRAK-4 deficiency are susceptible to invasive bacterial infections but have so far not been reported to be susceptible to viral infection. Blood cells from these patients are impaired in their ability to make TNF-alpha in response to activation by TLRs. A recent report has described concomitant impairment of type I IFN production after activation of TLRs 7, 8, and 9, but not TLR3. OBJECTIVES: We sought to evaluate the role of IRAK-4 in TLR-induced production of the type I IFN, IFN-alpha, in humans. METHODS: We examined TLR-induced production of TNF-alpha and IFN-alpha in PBMCs from an IRAK-4-deficient patient, his heterozygous carrier parents, and normal controls. RESULTS: TNF-alpha production in response to TLR agonists was severely impaired in the patient. IFN-alpha production induced by TLR7, TLR8, and TLR9, as well as TLR3 agonists, was low or absent. CONCLUSIONS: IRAK-4 plays an important role in the production of type I IFN, as well as TNF-alpha, induced by all TLRs, including TLR3. CLINICAL IMPLICATIONS: IRAK-4 may play a broader role in human innate antiviral immunity than previously appreciated.

Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor-dependent innate antiviral immune responses. Publishing Authors By Initials

DR McDonald,D Brown,FA Bonilla,RS Geha,

For similar virus diseases research abstracts see: virus diseases research

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Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor-dependent innate antiviral immune responses. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of allergy and clinical immunology

VOLUME: 118

Page Numbers: 1357-62

Journal Abbreviation: J. Allergy Clin. Immunol.

ISSN: 0091-6749

DAY: 25

MONTH: 09

YEAR: 2006

Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor-dependent innate antiviral immune responses. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 1275002

Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor-dependent innate antiviral immune responses. Keywords Mesh Terms:

KEYWORDS: Virus Diseases

MESH TERMS: immunology

Chemical & Substance for Abstract: Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor-dependent innate antiviral immune responses. Information

Substance Name: Interleukin-1 Receptor-Associated Kinase

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor-dependent innate antiviral immune responses.

AFFILIATION: Division of Immunology, Children's Hospital Boston, Boston, MA 02115, USA.

Country: United States

AGENCY: United States NIAID

GRANT: T32AI0075512

ACRONYM: AI

MEDLINETA: J Allergy Clin Immunol

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