ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Complete dependence on IRAK4 kinase activity in TLR2, but not TLR4, signaling pathways underlies decreased cytokine production and increased susceptibility to Streptococcus pneumoniae infection in IRAK4 kinase-inactive mice.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Targeted Lipid Metabolism Screening Uncovers Regulatory Effects on the STING Immune Response in Mevalonate, Eicosanoid and Fatty Acid Pathways.bioRxiv : the preprint server for biology · 2026Article
- Targeted lipid metabolism screening uncovers regulatory effects on the STING immune response in mevalonate, eicosanoid and fatty acid pathways.Frontiers in immunology · 2026Article
- ER-transiting bacterial toxins amplify STING innate immune responses and elicit ER stress.Infection and immunity · 2024Article
- The IRAK1/IRF5 axis initiates IL-12 response by dendritic cells and control of Toxoplasma gondii infection.Cell reports · 2024Article
- Porphyromonas gingivalis induction of TLR2 association with Vinculin enables PI3K activation and immune evasion.PLoS pathogens · 2023Article
- Regulation of innate immune signaling by IRAK proteins.Frontiers in immunology · 2023Review
- The IRAK-M death domain: a tale of three surfaces.Frontiers in molecular biosciences · 2023Article
- Post-Transcriptional Control of mRNA Metabolism and Protein Secretion: The Third Level of Regulation within the NF-κB System.Biomedicines · 2022Review
- The IRAK4 scaffold integrates TLR4-driven TRIF and MYD88 signaling pathways.Cell reports · 2022Article
- Efficacy of Sishen Wan on dinitrobenzene sulfonic acid-induced ulcerative colitis and its effect on toll-like receptor 2/interleukin-1 receptor-associated kinase-4/nuclear factor-κB signal pathway.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2022Article
- Mechanism of the fungal-like particles in the inhibition of adipogenesis in 3T3-L1 adipocytes.Scientific reports · 2021Article
- Classically activated mouse macrophages produce methylglyoxal that induces a TLR4- and RAGE-independent proinflammatory response.Journal of leukocyte biology · 2021Article
- Phosphorylation of Microglial IRF5 and IRF4 by IRAK4 Regulates Inflammatory Responses to Ischemia.Cells · 2021Article
- Article
- Oleanolic Acid Acetate Alleviates Symptoms of Experimental Autoimmune Encephalomyelitis in Mice by Regulating Toll-Like Receptor 2 Signaling.Frontiers in pharmacology · 2020Article
- Article
- Influenza "Trains" the Host for Enhanced Susceptibility to Secondary Bacterial Infection.mBio · 2019Article
- IRAK4 activity controls immune responses to intracellular bacteria Listeria monocytogenes and Mycobacterium smegmatis.Journal of leukocyte biology · 2018Article
- The θ-defensin retrocyclin 101 inhibits TLR4- and TLR2-dependent signaling and protects mice against influenza infection.Journal of leukocyte biology · 2017Article
- Deficiency in IRAK4 activity attenuates manifestations of murine Lupus.European journal of immunology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
IRAK4 is critical for MyD88-dependent TLR signaling, and patients with Irak4 mutations are extremely susceptible to recurrent bacterial infections. In these studies, mice homozygous for a mutant IRAK4 that lacks kinase activity (IRAK4(KDKI)) were used to address the role of IRAK4 in response to TLR agonists or bacterial infection. IRAK4(KDKI) macrophages exhibited diminished responsiveness to the TLR4 agonist LPS and little to no response to the TLR2 agonist Pam3Cys compared with wild-type macrophages as measured by cytokine mRNA, cytokine protein expression, and MAPK activation. Importantly, we identified two kinases downstream of the MAPKs, MNK1 and MSK1, whose phosphorylation is deficient in IRAK4(KDKI) macrophages stimulated through either TLR2 or TLR4, suggesting that IRAK4 contributes to TLR signaling beyond the initial phosphorylation of MAPKs. Additionally, IRAK4(KDKI) macrophages produced minimal cytokine mRNA expression in response to the Gram-positive bacteria Streptococcus pneumoniae and Staphylococcus aureus compared with WT cells, and IRAK4(KDKI) mice exhibited increased susceptibility and decreased cytokine production in vivo upon S. pneumoniae infection. Treatment of infected mice with a complex of polyinosinic-polycytidylic acid with poly-L-lysine and carboxymethyl cellulose (Hiltonol), a potent TLR3 agonist, significantly improved survival of both WT and IRAK4(KDKI) mice, thereby providing a potential treatment strategy in both normal and immunocompromised patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.