ArticleThe Journal of clinical investigation2006
Sepsis-induced suppression of lung innate immunity is mediated by IRAK-M.
Article in The Journal of clinical investigation, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
144 citing papers in PubMed, 2 syntheses or guidelines pooled it, 224 citations in OpenAlex.
- Pooled it
- Pooled it
- Steroid hormone ouabain cooperates with NaActa pharmaceutica Sinica. B · 2026Article
- Identification and Validation of Liver Transplantation-Induced Acute Lung Injury Biomarkers Using a Bioinformatics and Experimental Approach.Annals of transplantation · 2026Article
- Inhibiting METTL3 in macrophages alleviates colitis by enhancing M2 polarization via upregulating IRAKM.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- TNF superfamily member 14 drives post-influenza depletion of alveolar macrophages, enabling secondary pneumococcal pneumonia.The Journal of clinical investigation · 2026Article
- Sepsis-induced inflammasome impairment facilitates development of secondaryEmerging microbes & infections · 2025Article
- NUDT21 Regulates Macrophage Cytokine Responses via Alternative Polyadenylation in ARDS.Research square · 2025Article
- Precision treatment of ventilator-induced lung injury through alveolar epithelial cell targeted lipid nanoparticle delivery.Theranostics · 2025Article
- Recent advances in understanding oxidative stress in sepsis: pathogenic roles and antioxidant therapeutic prospects - a narrative review.Frontiers in pharmacology · 2025Review
- Lung immune incompetency after mild peritoneal sepsis and its partial restoration by type 1 interferon: a mouse model study.Intensive care medicine experimental · 2024Article
- Inflammatory disease status and response to TNF blockade are associated with mechanisms of endotoxin tolerance.Journal of autoimmunity · 2024Article
- IRAK-M Ablation Promotes Status Epilepticus-Induced Neuroinflammation via Activating M1 Microglia and Impairing Excitatory Synaptic Function.Molecular neurobiology · 2023Article
- NFATc3 Promotes Pulmonary Inflammation and Fibrosis by Regulating Production of CCL2 and CXCL2 in Macrophages.Aging and disease · 2023Article
- Acyloxyacyl hydrolase promotes pulmonary defense by preventing alveolar macrophage tolerance.PLoS pathogens · 2023Article
- IRAK-M has effects in regulation of lung epithelial inflammation.Respiratory research · 2023Article
- IRAK-M Regulates Proliferative and Invasive Phenotypes of Lung Fibroblasts.Inflammation · 2023Article
- NLRC3 expression in macrophage impairs glycolysis and host immune defense by modulating the NF-κB-NFAT5 complex during septic immunosuppression.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Role of toll-like receptors and nod-like receptors in acute lung infection.Frontiers in immunology · 2023Review
- The IRAK-M death domain: a tale of three surfaces.Frontiers in molecular biosciences · 2023Article
84 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Sepsis results in a state of relative immunosuppression, rendering critically ill patients susceptible to secondary infections and increased mortality. Monocytes isolated from septic patients and experimental animals display a "deactivated" phenotype, characterized by impaired inflammatory and antimicrobial responses, including hyporesponsiveness to LPS. We investigated the role of the LPS/TLR4 axis and its inhibitor, IL-1 receptor-associated kinase-M (IRAK-M), in modulating the immunosuppression of sepsis using a murine model of peritonitis-induced sepsis followed by secondary challenge by intratracheal Pseudomonasaeruginosa. Septic mice demonstrated impaired alveolar macrophage function and increased mortality when challenged with intratracheal Pseudomonas as compared with nonseptic controls. TLR2 and TLR4 expression was unchanged in the lung following sepsis, whereas levels of IRAK-M were upregulated. Macrophages from IRAK-M-deficient septic mice produced higher levels of proinflammatory cytokines ex vivo and greater costimulatory molecule expression in vivo as compared with those of their WT counterparts. Following sepsis and secondary intrapulmonary bacterial challenge, IRAK-M(-/-) animals had higher survival rates and improved bacterial clearance from lung and blood compared with WT mice. In addition, increased pulmonary chemokine and inflammatory cytokine production was observed in IRAK-M(-/-) animals, leading to enhanced neutrophil recruitment to airspaces. Collectively, these findings indicate that IRAK-M mediates critical aspects of innate immunity that result in an immunocompromised state during sepsis.
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What OpenQuestion holds
Registered trials
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.