ArticleProceedings of the National Academy of Sciences of the United States of America2009
Regulation of chemokine receptor by Toll-like receptor 2 is critical to neutrophil migration and resistance to polymicrobial sepsis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.
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Who cites it
134 citing papers in PubMed, 1 synthesis or guideline pooled it, 308 citations in OpenAlex.
- Neutrophil activity in sepsis: a systematic review.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2020Pooled it
- Innate immune deficiency of extremely premature neonates can be reversed by interferon-γ.PloS one · 2012Trial
- Identification of novel sepsis-related neutrophil subsets and surface markers for clinical diagnosis and outcome.Virulence · 2026Article
- TLR Signaling Beyond Immunity: Emerging Roles in Cell Migration, Metabolism, Development, and Host-Microbiome Crosstalk.Biology · 2026Review
- Comorbidities and Inflammation: How Chronic Diseases Prime the Host Response in Sepsis.International journal of molecular sciences · 2026Review
- Epigenetic regulation of neutrophil dysfunction in sepsis: mechanisms, biomarkers, and translational challenges.Journal of translational medicine · 2026Review
- Targeting IL-33 in COPD: mechanistic lessons from clinical trials and the path forward.Respiratory research · 2026Review
- Article
- Neutrophil in sepsis: functional aberration and regulated cell death.Frontiers in immunology · 2026Review
- Neutrophil extracellular traps and acute kidney injury: a narrative review.Frontiers in immunology · 2026Review
- Neutrophil and neutrophil extracellular traps in acute kidney injury: from mechanisms to treatments.Frontiers in immunology · 2025Review
- Neutrophil diversity and function in health and disease.Signal transduction and targeted therapy · 2024Review
- A narrative review of chemokine receptors CXCR1 and CXCR2 and their role in acute respiratory distress syndrome.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Interleukin-33: A Double-Edged Sword in Sepsis.Translational perioperative and pain medicine · 2024Article
- Heterogeneity of immune cells and their communications unveiled by transcriptome profiling in acute inflammatory lung injury.Frontiers in immunology · 2024Article
- [Inertial label-free sorting and chemotaxis of polymorphonuclear neutrophil in sepsis patients based on microfluidic technology].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2023Article
- Dietary Curcumin Modulating Effect on Performance, Antioxidant Status, and Immune-Related Response of Broiler Chickens Exposed to Imidacloprid Insecticide.Animals : an open access journal from MDPI · 2023Article
- Arntl deficiency in myeloid cells reduces neutrophil recruitment and delays skeletal muscle repair.Scientific reports · 2023Article
- Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation.JCI insight · 2023Article
- Review
74 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with sepsis have a marked defect in neutrophil migration. Here we identify a key role of Toll-like receptor 2 (TLR2) in the regulation of neutrophil migration and resistance during polymicrobial sepsis. We found that the expression of the chemokine receptor CXCR2 was dramatically down-regulated in circulating neutrophils from WT mice with severe sepsis, which correlates with reduced chemotaxis to CXCL2 in vitro and impaired migration into an infectious focus in vivo. TLR2 deficiency prevented the down-regulation of CXCR2 and failure of neutrophil migration. Moreover, TLR2(-/-) mice exhibited higher bacterial clearance, lower serum inflammatory cytokines, and improved survival rate during severe sepsis compared with WT mice. In vitro, the TLR2 agonist lipoteichoic acid (LTA) down-regulated CXCR2 expression and markedly inhibited the neutrophil chemotaxis and actin polymerization induced by CXCL2. Moreover, neutrophils activated ex vivo by LTA and adoptively transferred into naïve WT recipient mice displayed a significantly reduced competence to migrate toward thioglycolate-induced peritonitis. Finally, LTA enhanced the expression of G protein-coupled receptor kinases 2 (GRK2) in neutrophils; increased expression of GRK2 was seen in blood neutrophils from WT mice, but not TLR2(-/-) mice, with severe sepsis. Our findings identify an unexpected detrimental role of TLR2 in polymicrobial sepsis and suggest that inhibition of TLR2 signaling may improve survival from sepsis.
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