ArticleThe Journal of clinical investigation2015
Inflammation drives thrombosis after Salmonella infection via CLEC-2 on platelets.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 169 citations in OpenAlex.
- Comparison of variably specific Bruton tyrosine kinase inhibitors on platelet aggregation mediated by Fcγ receptor (FcγR) IIa, glycoprotein VI, and platelet endothelial aggregation receptor (PEAR) 1: implications for Bruton tyrosine kinase inhibitors as antithrombotic therapy.Research and practice in thrombosis and haemostasis · 2026Article
- Vaccine-induced antibodies can limitmBio · 2026Article
- Proximal lower-limb septic deep vein thrombosis contiguous with salmonella arteritis: a case report.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Article
- Physical Signs and Hematological and Biochemical Alterations in Salmonella-Plasmodium Sequentially Coinfected Albino Wistar Rats.TheScientificWorldJournal · 2026Article
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Sepsis-induced immunothrombosis: from cellular crosstalk to multiple organ dysfunction.Frontiers in immunology · 2026Review
- Salmonella-Induced Immunothrombosis: An Unusual Case of Pulmonary Embolism in the Setting of Enteric Infection.Cureus · 2025Article
- Beyond hemostasis, the immunomodulatory nature of platelets.Research and practice in thrombosis and haemostasis · 2025Review
- Article
- Evaluation of the podoplanin/C-type lectin-like receptor-2 (CLEC-2) pathway as a mediator of platelet and coagulation activation in sickle cell disease.Research and practice in thrombosis and haemostasis · 2025Article
- Influence of homocysteine on regulating immunothrombosis: mechanisms and therapeutic potential in management of infections.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Review
- Article
- Discrete and conserved inflammatory signatures drive thrombosis in different organs after Salmonella infection.Nature communications · 2025Article
- Podoplanin and microthrombi in lung injury.Blood vessels, thrombosis & hemostasis · 2025Article
- The C3/C3aR pathway exacerbates acetaminophen-induced mouse liver injury via upregulating podoplanin on the macrophage.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Okra polysaccharide mitigates carrageenan-induced thrombosis in mice by regulating inflammation and oxidative stress.Frontiers in pharmacology · 2025Article
- Platelet aggregation responses toPlatelets · 2024Article
- Btk inhibition: the importance of being selective.Blood advances · 2024Article
- Selective Btk inhibition by PRN1008/PRN473 blocks human CLEC-2, and PRN473 reduces venous thrombosis formation in mice.Blood advances · 2024Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 4 institutions in 4 countries.
Funding
Abstract
Thrombosis is a common, life-threatening consequence of systemic infection; however, the underlying mechanisms that drive the formation of infection-associated thrombi are poorly understood. Here, using a mouse model of systemic Salmonella Typhimurium infection, we determined that inflammation in tissues triggers thrombosis within vessels via ligation of C-type lectin-like receptor-2 (CLEC-2) on platelets by podoplanin exposed to the vasculature following breaching of the vessel wall. During infection, mice developed thrombi that persisted for weeks within the liver. Bacteria triggered but did not maintain this process, as thrombosis peaked at times when bacteremia was absent and bacteria in tissues were reduced by more than 90% from their peak levels. Thrombus development was triggered by an innate, TLR4-dependent inflammatory cascade that was independent of classical glycoprotein VI-mediated (GPVI-mediated) platelet activation. After infection, IFN-γ release enhanced the number of podoplanin-expressing monocytes and Kupffer cells in the hepatic parenchyma and perivascular sites and absence of TLR4, IFN-γ, or depletion of monocytic-lineage cells or CLEC-2 on platelets markedly inhibited the process. Together, our data indicate that infection-driven thrombosis follows local inflammation and upregulation of podoplanin and platelet activation. The identification of this pathway offers potential therapeutic opportunities to control the devastating consequences of infection-driven thrombosis without increasing the risk of bleeding.
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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.