Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA – J Am Med Assoc. 2016;315:801 https://doi.org/10.1001/jama.2016.0287.
Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet. 2020;395:200–11. https://doi.org/10.1016/S0140-6736(19)32989-7.
Fleischmann C, Scherag A, Adhikari NKJ, Hartog CS, Tsaganos T, Schlattmann P, et al. Assessment of global incidence and mortality of hospital-treated sepsis current estimates and limitations. Am J Respir Crit Care Med. 2016;193:259–72. https://doi.org/10.1164/rccm.201504-0781OC.
Mostel Z, Perl A, Marck M, Mehdi SF, Lowell B, Bathija S, et al. Post-sepsis syndrome- An evolving entity that afflicts survivors of sepsis. Mol Med. 2019;26:6 https://doi.org/10.1186/s10020-019-0132-z.
Marshall JC. Why have clinical trials in sepsis failed? Trends Mol Med. 2014;20:195–203. https://doi.org/10.1016/j.molmed.2014.01.007.
Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med. 2021;49:1974–82. https://doi.org/10.1097/CCM.0000000000005337.
Martín-Fernández M, Tamayo-Velasco Á, Aller R, Gonzalo-Benito H, Martínez-Paz P, Tamayo E. Endothelial dysfunction and neutrophil degranulation as central events in sepsis physiopathology. Int J Mol Sci. 2021;22:6272 https://doi.org/10.3390/ijms22126272.
De Giovanni M, Tam H, Valet C, Xu Y, Looney MR, Cyster JG. GPR35 promotes neutrophil recruitment in response to serotonin metabolite 5-HIAA. Cell. 2022;185:1103–4. https://doi.org/10.1016/j.cell.2022.01.010.
Rosa BA, Ahmed M, Singh DK, Choreño-Parra JA, Cole J, Jiménez-Álvarez LA, et al. IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection. Commun Biol. 2021;4:290 https://doi.org/10.1038/s42003-021-01829-4.
Alsabani M, Abrams ST, Cheng Z, Morton B, Lane S, Alosaimi S, et al. Reduction of NETosis by targeting CXCR1/2 reduces thrombosis, lung injury, and mortality in experimental human and murine sepsis. Br J Anaesth. 2022;128:283–93. https://doi.org/10.1016/j.bja.2021.10.039.
Sônego F, Castanheira FVS, Ferreira RG, Kanashiro A, Leite CAVG, Nascimento DC, et al. Paradoxical roles of the neutrophil in sepsis: protective and deleterious. Front Immunol. 2016;7:155. https://doi.org/10.3389/fimmu.2016.00155.
Barkaway A, Rolas L, Joulia R, Bodkin J, Lenn T, Owen-Woods C, et al. Age-related changes in the local milieu of inflamed tissues cause aberrant neutrophil trafficking and subsequent remote organ damage. Immunity. 2021;54:1494–1510.e7. https://doi.org/10.1016/j.immuni.2021.04.025.
Polet F, Feron O. Endothelial cell metabolism and tumour angiogenesis: Glucose and glutamine as essential fuels and lactate as the driving force. J Intern Med. 2013;273:156–65. https://doi.org/10.1111/joim.12016.
Folco EJ, Mawson TL, Vromman A, Bernardes-Souza B, Franck G, Persson O, et al. Neutrophil extracellular traps induce endothelial cell activation and tissue factor production through interleukin-1α and cathepsin G. ArteriosclerThrombVasc Biol. 2018;38:1901–12. https://doi.org/10.1161/ATVBAHA.118.311150.
Joffre J, Hellman J, Ince C, Ait-Oufella H. Endothelial responses in sepsis. Am J Respiratory Crit Care Med. 2020;202:361–70. https://doi.org/10.1164/rccm.201910-1911TR.
Papalexi E, Satija R. Single-cell RNA sequencing to explore immune cell heterogeneity. Nat Rev Immunol. 2018;18:35–45. https://doi.org/10.1038/nri.2017.76.
Qi X, Yu Y, Sun R, Huang J, Liu L, Yang Y, et al. Identification and characterization of neutrophil heterogeneity in sepsis. Crit Care. 2021;25:50. https://doi.org/10.1186/s13054-021-03481-0.
Xu X, Hua X, Mo H, Hu S, Song J. Single-cell RNA sequencing to identify cellular heterogeneity and targets in cardiovascular diseases: from bench to bedside. Basic Res Cardiol. 2023;118:7. https://doi.org/10.1007/s00395-022-00972-1.
Qiu X, Li J, Bonenfant J, Jaroszewski L, Mittal A, Klein W, et al. Dynamic changes in human single-cell transcriptional signatures during fatal sepsis. J Leukoc Biol. 2021;110:1253–68. https://doi.org/10.1002/JLB.5MA0721-825R.
Scicluna BP, Klein Klouwenberg PMC, Van Vught LA, Wiewel MA, Ong DSY, Zwinderman AH, et al. A molecular biomarker to diagnose community-acquired pneumonia on intensive care unit admission. Am J Respir Crit Care Med. 2015;192:826–35. https://doi.org/10.1164/rccm.201502-0355OC.
Jin S, Guerrero-Juarez CF, Zhang L, Chang I, Ramos R, Kuan CH, et al. Inference and analysis of cell-cell communication using CellChat. Nat Commun. 2021;12:1088. https://doi.org/10.1038/s41467-021-21246-9.
Qiu X, Mao Q, Tang Y, Wang L, Chawla R, Pliner HA, et al. Reversed graph embedding resolves complex single-cell trajectories. Nat Methods. 2017;14:979–82. https://doi.org/10.1038/nmeth.4402.
Hänzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-Seq data. BMC Bioinforma. 2013;14:7. https://doi.org/10.1186/1471-2105-14-7.
Tsuda Y, Takahashi H, Kobayashi M, Hanafusa T, Herndon DN, Suzuki F. Three different neutrophil subsets exhibited in mice with different susceptibilities to infection by methicillin-resistant Staphylococcus aureus. Immunity. 2004;21:215–26. https://doi.org/10.1016/j.immuni.2004.07.006.
Castanheira FVS, Kubes P. Neutrophils and NETs in modulating acute and chronic inflammation. Blood. 2019;133:2178–85. https://doi.org/10.1182/blood-2018-11-844530.
Van Der Poll T, Van De Veerdonk FL, Scicluna BP, Netea MG. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol. 2017;17:407–20. https://doi.org/10.1038/nri.2017.36.
van der Poll T, Opal SM. Host-pathogen interactions in sepsis. Lancet Infect Dis. 2008;8:32–43. https://doi.org/10.1016/S1473-3099(07)70265-7.
McDonald B, Davis RP, Kim SJ, Tse M, Esmon CT, Kolaczkowska E, et al. Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice. Blood. 2017;129:1357–67. https://doi.org/10.1182/blood-2016-09-741298.
Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med. 2007;13:463–9. https://doi.org/10.1038/nm1565.
Wang Q, Long G, Luo H, Zhu X, Han Y, Shang Y, et al. S100A8/A9: An emerging player in sepsis and sepsis-induced organ injury. Biomed Pharmacother. 2023;168:115674 https://doi.org/10.1016/j.biopha.2023.115674.
Arslan F, Smeets MB, O’Neill LAJ, Keogh B, McGuirk P, Timmers L, et al. Myocardial ischemia/reperfusion injury is mediated by leukocytic toll-like receptor-2 and reduced by systemic administration of a novel anti-toll-like receptor-2 antibody. Circulation. 2010;121:80–90. https://doi.org/10.1161/CIRCULATIONAHA.109.880187.
Selejan S, Poss J, Walter F, Hohl M, Kaiser R, Kazakov A, et al. Ischaemia-induced up-regulation of Toll-like receptor 2 in circulating monocytes in cardiogenic shock. Eur Heart J. 2012;33:1085–94. https://doi.org/10.1093/eurheartj/ehr377.
Mulfaul K, Ozaki E, Fernando N, Brennan K, Chirco KR, Connolly E, et al. Toll-like receptor 2 facilitates oxidative damage-induced retinal degeneration. Cell Rep. 2020;30:2209–2224.e5. https://doi.org/10.1016/j.celrep.2020.01.064.
Torres LK, Pickkers P, Van Der Poll T. Sepsis-Induced Immunosuppression. Annu Rev Physiol. 2022;84:157–81. https://doi.org/10.1146/annurev-physiol-061121-040214.
Ong DSY, Bonten MJM, Spitoni C, Verduyn Lunel FM, Frencken JF, Horn J, et al. Epidemiology of multiple herpes viremia in previously immunocompetent patients with septic shock. Clin Infect Dis. 2017;64:1204–10. https://doi.org/10.1093/cid/cix120.
Walton AH, Muenzer JT, Rasche D, Boomer JS, Sato B, Brownstein BH, et al. Reactivation of multiple viruses in patients with sepsis. PLoS One. 2014;9:e98819 https://doi.org/10.1371/journal.pone.0098819.
Padovani CM, Yin K. Immunosuppression in sepsis: biomarkers and specialized pro-resolving mediators. Biomedicines. 2024;12:175 https://doi.org/10.3390/biomedicines12010175.
Davies R, O’Dea K, Gordon A. Immune therapy in sepsis: are we ready to try again? J Intensive Care Soc. 2018;19:326–44. https://doi.org/10.1177/1751143718765407.
Leijte GP, Rimmelé T, Kox M, Bruse N, Monard C, Gossez M, et al. Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes. Crit Care. 2020;24:110. https://doi.org/10.1186/s13054-020-2830-x.
Cour-Andlauer F, Morrow BM, McCulloch M, Javouhey E, Lecour S, Van As S, et al. Decreased human leukocyte antigen DR on circulating monocytes expression after severe pediatric trauma: an exploratory report. Pediatr Crit Care Med. 2021;22:e314–e323. https://doi.org/10.1097/PCC.0000000000002604.
Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, et al. Polarization of tumor-associated neutrophil phenotype by TGF-β: “N1” versus “N2” TAN. Cancer Cell. 2009;16:183–94. https://doi.org/10.1016/j.ccr.2009.06.017.
Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Investig. 2012;122:787–95. https://doi.org/10.1172/JCI59643.
Pillay J, Kamp VM, Van Hoffen E, Visser T, Tak T, Lammers JW, et al. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1. J Clin Investig. 2012;122:327–36. https://doi.org/10.1172/JCI57990.
Pan T, Sun S, Chen Y, Tian R, Chen E, Tan R, et al. Immune effects of PI3K/Akt/HIF-1α-regulated glycolysis in polymorphonuclear neutrophils during sepsis. Crit Care. 2022;26:29. https://doi.org/10.1186/s13054-022-03893-6.
Peyssonnaux C, Cejudo-Martin P, Doedens A, Zinkernagel AS, Johnson RS, Nizet V. Cutting edge: essential role of hypoxia inducible factor-1α in development of lipopolysaccharide-induced sepsis. J Immunol. 2007;178:7516–9. https://doi.org/10.4049/jimmunol.178.12.7516.
Portier I, Campbell RA. Role of Platelets in Detection and Regulation of Infection. Arterioscler Thromb Vasc Biol. 2021;41:70–8. https://doi.org/10.1161/ATVBAHA.120.314645.
Shannon O. The role of platelets in sepsis. Res PractThrombHaemost. 2021;5:27–37. https://doi.org/10.1002/rth2.12465.
Middleton EA, Rowley JW, Campbell RA, Grissom CK, Brown SM, Beesley SJ, et al. Sepsis alters the transcriptional and translational landscape of human and murine platelets. Blood. 2019;134:911–23. https://doi.org/10.1182/blood.2019000067.
Rørvig S, Østergaard O, Heegaard NHH, Borregaard N. Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane: correlation with transcriptome profiling of neutrophil precursors. J Leukoc Biol. 2013;94:711–21. https://doi.org/10.1189/jlb.1212619.
Qu Y, Zhang X, Qiao R, Di F, Song Y, Wang J, et al. Blood FOLR3 methylation dysregulations and heterogeneity in non-small lung cancer highlight its strong associations with lung squamous carcinoma. Respir Res. 2024;25:59 https://doi.org/10.1186/s12931-024-02691-8.
Yuan Y, Nymoen DA, Dong HP, Bjørang O, Shih IM, Low PS, et al. Expression of the folate receptor genes FOLR1 and FOLR3 differentiates ovarian carcinoma from breast carcinoma and malignant mesothelioma in serous effusions. Hum Pathol. 2009;40:1453–60. https://doi.org/10.1016/j.humpath.2009.02.013.
Flerlage T, Crawford JC, Allen EK, Severns D, Tan S, Surman S, et al. Single cell transcriptomics identifies distinct profiles in pediatric acute respiratory distress syndrome. Nat Commun. 2023;14:3870. https://doi.org/10.1038/s41467-023-39593-0.