Acknowledgement
This research is funded by grants from the NIH (R01HL147525, M.K.).
References
- Rhee C, Dantes R, Epstein L, Murphy DJ, Seymour CW, Iwashyna TJ, Kadri SS, Angus DC, Danner RL, Fiore AE, et al. Incidence and trends of sepsis in us hospitals using clinical vs claims data, 2009-2014. JAMA 2017;318:1241-1249. https://doi.org/10.1001/jama.2017.13836
- Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet 2020;395:200-211. https://doi.org/10.1016/S0140-6736(19)32989-7
- Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992;101:1644-1655. https://doi.org/10.1378/chest.101.6.1644
- Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 2016;315:801-810. https://doi.org/10.1001/jama.2016.0287
- Jeganathan N, Yau S, Ahuja N, Otu D, Stein B, Fogg L, Balk R. The characteristics and impact of source of infection on sepsis-related ICU outcomes. J Crit Care 2017;41:170-176. https://doi.org/10.1016/j.jcrc.2017.05.019
- Sinha M, Jupe J, Mack H, Coleman TP, Lawrence SM, Fraley SI. Emerging technologies for molecular diagnosis of sepsis. Clin Microbiol Rev 2018;31:e00089-17.
- Miller RR 3rd, Lopansri BK, Burke JP, Levy M, Opal S, Rothman RE, D'Alessio FR, Sidhaye VK, Aggarwal NR, Balk R, et al. Validation of a host response assay, septicyte lab, for discriminating sepsis from systemic inflammatory response syndrome in the ICU. Am J Respir Crit Care Med 2018;198:903-913. https://doi.org/10.1164/rccm.201712-2472OC
- Rhee C, Kadri SS, Danner RL, Suffredini AF, Massaro AF, Kitch BT, Lee G, Klompas M. Diagnosing sepsis is subjective and highly variable: a survey of intensivists using case vignettes. Crit Care 2016;20:89.
- Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, Lemeshow S, Osborn T, Terry KM, Levy MM. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med 2017;376:2235-2244. https://doi.org/10.1056/NEJMoa1703058
- Kahn JM, Davis BS, Yabes JG, Chang CH, Chong DH, Hershey TB, Martsolf GR, Angus DC. Association between state-mandated protocolized sepsis care and in-hospital mortality among adults with sepsis. JAMA 2019;322:240-250. https://doi.org/10.1001/jama.2019.9021
- Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med 2017;45:486-552. https://doi.org/10.1097/CCM.0000000000002255
- Angus DC. The search for effective therapy for sepsis: back to the drawing board? JAMA 2011;306:2614-2615. https://doi.org/10.1001/jama.2011.1853
- Liu VX, Fielding-Singh V, Greene JD, Baker JM, Iwashyna TJ, Bhattacharya J, Escobar GJ. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med 2017;196:856-863. https://doi.org/10.1164/rccm.201609-1848OC
- Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34:1589-1596. https://doi.org/10.1097/01.CCM.0000217961.75225.E9
- Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, Rubenfeld G, Kahn JM, ShankarHari M, Singer M, et al. Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 2016;315:762-774. https://doi.org/10.1001/jama.2016.0288
- Cho SY, Choi JH. Biomarkers of sepsis. Infect Chemother 2014;46:1-12. https://doi.org/10.3947/ic.2014.46.1.1
- Henriquez-Camacho C, Losa J. Biomarkers for sepsis. BioMed Res Int 2014;2014:547818.
- Anush MM, Ashok VK, Sarma RI, Pillai SK. Role of C-reactive protein as an indicator for determining the outcome of sepsis. Indian J Crit Care Med 2019;23:11-14. https://doi.org/10.5005/jp-journals-10071-23105
- Mustafic S, Brkic S, Prnjavorac B, Sinanovic A, Porobic Jahic H, Salkic S. Diagnostic and prognostic value of procalcitonin in patients with sepsis. Med Glas (Zenica) 2018;15:93-100. https://doi.org/10.17392/963-18
- Yunus I, Fasih A, Wang Y. The use of procalcitonin in the determination of severity of sepsis, patient outcomes and infection characteristics. PLoS One 2018;13:e0206527.
- Szederjesi J, Almasy E, Lazar A, Hutanu A, Badea I, Georgescu A. An evaluation of serum procalcitonin and c-reactive protein levels as diagnostic and prognostic biomarkers of severe sepsis. J Crit Care Med (Targu Mures) 2015;1:147-153. https://doi.org/10.1515/jccm-2015-0022
- Chousterman BG, Boissonnas A, Poupel L, Baudesson de Chanville C, Adam J, Tabibzadeh N, Licata F, Lukaszewicz AC, Lombes A, Deterre P, et al. Ly6chigh monocytes protect against kidney damage during sepsis via a CX3CR1-dependent adhesion mechanism. J Am Soc Nephrol 2016;27:792-803. https://doi.org/10.1681/ASN.2015010009
- Xiu F, Stanojcic M, Wang V, Qi P, Jeschke MG. C-C chemokine receptor type 2 expression on monocytes before sepsis onset is higher than that of postsepsis in septic burned patients: a new predictor for sepsis in burned injury. Ann Surg 2016;264:392-398. https://doi.org/10.1097/SLA.0000000000001531
- Nemeth ZH, Bilaniuk JW, Di Fazio LT, Paglinco SR, Rolandelli RH. Chemokine receptor CCR2-expressing inflammatory monocytes contribute to the exacerbated inflammatory response associated with sepsis. J Am Coll Surg 2015;221:S40-S41. CROSSREF https://doi.org/10.1016/j.jamcollsurg.2015.07.083
- Pachot A, Cazalis MA, Venet F, Turrel F, Faudot C, Voirin N, Diasparra J, Bourgoin N, Poitevin F, Mougin B, et al. Decreased expression of the fractalkine receptor CX3CR1 on circulating monocytes as new feature of sepsis-induced immunosuppression. J Immunol 2008;180:6421-6429. https://doi.org/10.4049/jimmunol.180.9.6421
- Lerman YV, Lim K, Hyun YM, Falkner KL, Yang H, Pietropaoli AP, Sonnenberg A, Sarangi PP, Kim M. Sepsis lethality via exacerbated tissue infiltration and TLR-induced cytokine production by neutrophils is integrin α3β1-dependent. Blood 2014;124:3515-3523. https://doi.org/10.1182/blood-2014-01-552943
- Jamsa J, Ala-Kokko T, Huotari V, Ohtonen P, Savolainen ER, Syrjala H. Neutrophil CD64, C-reactive protein, and procalcitonin in the identification of sepsis in the ICU - Post-test probabilities. J Crit Care 2018;43:139-142. https://doi.org/10.1016/j.jcrc.2017.08.038
- Mahmoodpoor A, Paknezhad S, Shadvar K, Hamishehkar H, Movassaghpour AA, Sanaie S, Ghamari AA, Soleimanpour H. Flow cytometry of CD64, HLA-DR, CD25, and TLRs for diagnosis and prognosis of sepsis in critically ill patients admitted to the intensive care unit: a review article. Anesth Pain Med 2018;8:e83128.
- Faix JD. Biomarkers of sepsis. Crit Rev Clin Lab Sci 2013;50:23-36. https://doi.org/10.3109/10408363.2013.764490
- Moran JL, Santamaria J. Reconsidering lactate as a sepsis risk biomarker. PLoS One 2017;12:e0185320.
- Kang HE, Park DW. Lactate as a biomarker for sepsis prognosis? Infect Chemother 2016;48:252-253. https://doi.org/10.3947/ic.2016.48.3.252
- Ganesh K, Sharma RN, Varghese J, Pillai MG. A profile of metabolic acidosis in patients with sepsis in an Intensive Care Unit setting. Int J Crit Illn Inj Sci 2016;6:178-181. https://doi.org/10.4103/2229-5151.195417
- Zhang Z, Zhu C, Mo L, Hong Y. Effectiveness of sodium bicarbonate infusion on mortality in septic patients with metabolic acidosis. Intensive Care Med 2018;44:1888-1895. https://doi.org/10.1007/s00134-018-5379-2
- Povoa P, Almeida E, Moreira P, Fernandes A, Mealha R, Aragao A, Sabino H. C-reactive protein as an indicator of sepsis. Intensive Care Med 1998;24:1052-1056. https://doi.org/10.1007/s001340050715
- Wang HE, Shapiro NI, Safford MM, Griffin R, Judd S, Rodgers JB, Warnock DG, Cushman M, Howard G. High-sensitivity C-reactive protein and risk of sepsis. PLoS One 2013;8:e69232.
- Yeh CF, Wu CC, Liu SH, Chen KF. Comparison of the accuracy of neutrophil CD64, procalcitonin, and C-reactive protein for sepsis identification: a systematic review and meta-analysis. Ann Intensive Care 2019;9:5.
- Nargis W, Ibrahim M, Ahamed BU. Procalcitonin versus C-reactive protein: usefulness as biomarker of sepsis in ICU patient. Int J Crit Illn Inj Sci 2014;4:195-199. https://doi.org/10.4103/2229-5151.141356
- Wang H, Ward MF, Sama AE. Targeting HMGB1 in the treatment of sepsis. Expert Opin Ther Targets 2014;18:257-268. https://doi.org/10.1517/14728222.2014.863876
- Stevens NE, Chapman MJ, Fraser CK, Kuchel TR, Hayball JD, Diener KR. Therapeutic targeting of HMGB1 during experimental sepsis modulates the inflammatory cytokine profile to one associated with improved clinical outcomes. Sci Rep 2017;7:5850.
- Wang X, Li ZY, Zeng L, Zhang AQ, Pan W, Gu W, Jiang JX. Neutrophil CD64 expression as a diagnostic marker for sepsis in adult patients: a meta-analysis. Crit Care 2015;19:245.
- Lerman YV, Kim M. Neutrophil migration under normal and sepsis conditions. Cardiovasc Hematol Disord Drug Targets 2015;15:19-28. https://doi.org/10.2174/1871529X15666150108113236
- Sarangi PP, Hyun YM, Lerman YV, Pietropaoli AP, Kim M. Role of β1 integrin in tissue homing of neutrophils during sepsis. Shock 2012;38:281-287. https://doi.org/10.1097/SHK.0b013e31826136f8
- Ngo LY, Kasahara S, Kumasaka DK, Knoblaugh SE, Jhingran A, Hohl TM. Inflammatory monocytes mediate early and organ-specific innate defense during systemic candidiasis. J Infect Dis 2014;209:109-119. https://doi.org/10.1093/infdis/jit413
- Andonegui G, Zelinski EL, Schubert CL, Knight D, Craig LA, Winston BW, Spanswick SC, Petri B, Jenne CN, Sutherland JC, et al. Targeting inflammatory monocytes in sepsis-associated encephalopathy and long-term cognitive impairment. JCI Insight 2018;3:e99364.
- Trzeciak A, Lerman YV, Kim TH, Kim MR, Mai N, Halterman MW, Kim M. Long-term microgliosis driven by acute systemic inflammation. J Immunol 2019;203:2979-2989. https://doi.org/10.4049/jimmunol.1900317
- Lee M, Lee Y, Song J, Lee J, Chang SY. Tissue-specific role of CX3CR1 expressing immune cells and their relationships with human disease. Immune Netw 2018;18:e5.
- Friggeri A, Cazalis MA, Pachot A, Cour M, Argaud L, Allaouchiche B, Floccard B, Schmitt Z, Martin O, Rimmele T, et al.; MIP Rea Study Group. Decreased CX3CR1 messenger RNA expression is an independent molecular biomarker of early and late mortality in critically ill patients. Crit Care 2016;20:204.
- Ancuta P, Rao R, Moses A, Mehle A, Shaw SK, Luscinskas FW, Gabuzda D. Fractalkine preferentially mediates arrest and migration of CD16+ monocytes. J Exp Med 2003;197:1701-1707. https://doi.org/10.1084/jem.20022156
- Tan RS, Ho B, Leung BP, Ding JL. TLR cross-talk confers specificity to innate immunity. Int Rev Immunol 2014;33:443-453. https://doi.org/10.3109/08830185.2014.921164
- Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol 2014;5:461.
- Kanamaru T, Kamimura N, Yokota T, Nishimaki K, Iuchi K, Lee H, Takami S, Akashiba H, Shitaka Y, Ueda M, et al. Intravenous transplantation of bone marrow-derived mononuclear cells prevents memory impairment in transgenic mouse models of Alzheimer's disease. Brain Res 2015;1605:49-58. https://doi.org/10.1016/j.brainres.2015.02.011
- Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN, Hayden MS, Hieny S, Sutterwala FS, Flavell RA, Ghosh S, et al. TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science 2005;308:1626-1629.
- Matta BM, Reichenbach DK, Blazar BR, Turnquist HR. Alarmins and their receptors as modulators and indicators of alloimmune responses. Am J Transplant 2017;17:320-327. https://doi.org/10.1111/ajt.13887
- Kim YK, Shin JS, Nahm MH. Nod-like receptors in infection, immunity, and diseases. Yonsei Med J 2016;57:5-14. https://doi.org/10.3349/ymj.2016.57.1.5
- von Kugelgen I, Hoffmann K. Pharmacology and structure of P2Y receptors. Neuropharmacology 2016;104:50-61. https://doi.org/10.1016/j.neuropharm.2015.10.030
- Roh JS, Sohn DH. Damage-associated molecular patterns in inflammatory diseases. Immune Netw 2018;18:e27.
- Tidswell M, Tillis W, Larosa SP, Lynn M, Wittek AE, Kao R, Wheeler J, Gogate J, Opal SM; Eritoran Sepsis Study Group. Phase 2 trial of eritoran tetrasodium (E5564), a Toll-like receptor 4 antagonist, in patients with severe sepsis. Crit Care Med 2010;38:72-83. https://doi.org/10.1097/CCM.0b013e3181b07b78
- Rice TW, Wheeler AP, Bernard GR, Vincent JL, Angus DC, Aikawa N, Demeyer I, Sainati S, Amlot N, Cao C, et al. A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis. Crit Care Med 2010;38:1685-1694. https://doi.org/10.1097/CCM.0b013e3181e7c5c9
- Savva A, Roger T. Targeting Toll-like receptors: promising therapeutic strategies for the management of sepsis-associated pathology and infectious diseases. Front Immunol 2013;4:387.
- Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev 2009;22:240-273. https://doi.org/10.1128/CMR.00046-08
- Yanai H, Negishi H, Taniguchi T. The IRF family of transcription factors: Inception, impact and implications in oncogenesis. OncoImmunology 2012;1:1376-1386. https://doi.org/10.4161/onci.22475
- Nagar A, DeMarco RA, Harton JA. Inflammasome and caspase-1 activity characterization and evaluation: an imaging flow cytometer-based detection and assessment of inflammasome specks and caspase-1 activation. J Immunol 2019;202:1003-1015. https://doi.org/10.4049/jimmunol.1800973
- Nilsberth C, Elander L, Hamzic N, Norell M, Lonn J, Engstrom L, Blomqvist A. The role of interleukin-6 in lipopolysaccharide-induced fever by mechanisms independent of prostaglandin E2. Endocrinology 2009;150:1850-1860. https://doi.org/10.1210/en.2008-0806
- Aderka D. Role of tumor necrosis factor in the pathogenesis of intravascular coagulopathy of sepsis: potential new therapeutic implications. Isr J Med Sci 1991;27:52-60.
- Zeni F, Freeman B, Natanson C. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med 1997;25:1095-1100. https://doi.org/10.1097/00003246-199707000-00001
- Cohen J, Carlet J. INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. Crit Care Med 1996;24:1431-1440. https://doi.org/10.1097/00003246-199609000-00002
- Polk HC Jr, Cheadle WG, Livingston DH, Rodriguez JL, Starko KM, Izu AE, Jaffe HS, Sonnenfeld G. A randomized prospective clinical trial to determine the efficacy of interferon-gamma in severely injured patients. Am J Surg 1992;163:191-196. https://doi.org/10.1016/0002-9610(92)90099-D
- Mastellos DC, Ricklin D, Lambris JD. Clinical promise of next-generation complement therapeutics. Nat Rev Drug Discov 2019;18:707-729. https://doi.org/10.1038/s41573-019-0031-6
- Ricklin D, Reis ES, Lambris JD. Complement in disease: a defence system turning offensive. Nat Rev Nephrol 2016;12:383-401. https://doi.org/10.1038/nrneph.2016.70
- Markiewski MM, DeAngelis RA, Lambris JD. Complexity of complement activation in sepsis. J Cell Mol Med 2008;12:2245-2254. https://doi.org/10.1111/j.1582-4934.2008.00504.x
- Ram S, Lewis LA, Rice PA. Infections of people with complement deficiencies and patients who have undergone splenectomy. Clin Microbiol Rev 2010;23:740-780. https://doi.org/10.1128/CMR.00048-09
- Ricklin D, Lambris JD. New milestones ahead in complement-targeted therapy. Semin Immunol 2016;28:208-222. https://doi.org/10.1016/j.smim.2016.06.001
- Simmons J, Pittet JF. The coagulopathy of acute sepsis. Curr Opin Anaesthesiol 2015;28:227-236. https://doi.org/10.1097/ACO.0000000000000163
- Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 2013;13:34-45. https://doi.org/10.1038/nri3345
- Fiusa MM, Carvalho-Filho MA, Annichino-Bizzacchi JM, De Paula EV. Causes and consequences of coagulation activation in sepsis: an evolutionary medicine perspective. BMC Med 2015;13:105.
- Camicia G, Pozner R, de Larranaga G. Neutrophil extracellular traps in sepsis. Shock 2014;42:286-294. https://doi.org/10.1097/SHK.0000000000000221
- Iba T, Nagaoka I, Boulat M. The anticoagulant therapy for sepsis-associated disseminated intravascular coagulation. Thromb Res 2013;131:383-389. https://doi.org/10.1016/j.thromres.2013.03.012
- Iba T, Saito D, Wada H, Asakura H. Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: a prospective multicenter survey. Thromb Res 2012;130:e129-e133. https://doi.org/10.1016/j.thromres.2012.03.021
- Vincent JL, Francois B, Zabolotskikh I, Daga MK, Lascarrou JB, Kirov MY, Pettila V, Wittebole X, Meziani F, Mercier E, et al. Effect of a recombinant human soluble thrombomodulin on mortality in patients with sepsis-associated coagulopathy: the scarlet randomized clinical trial. JAMA 2019;321:1993-2002. https://doi.org/10.1001/jama.2019.5358
- Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 2013;13:159-175. https://doi.org/10.1038/nri3399
- Soehnlein O. Direct and alternative antimicrobial mechanisms of neutrophil-derived granule proteins. J Mol Med (Berl) 2009;87:1157-1164. https://doi.org/10.1007/s00109-009-0508-6
- Lakhan SE, Kirchgessner A, Tepper D, Leonard A. Matrix metalloproteinases and blood-brain barrier disruption in acute ischemic stroke. Front Neurol 2013;4:32.
- Chou SH, Feske SK, Simmons SL, Konigsberg RG, Orzell SC, Marckmann A, Bourget G, Bauer DJ, De Jager PL, Du R, et al. Elevated peripheral neutrophils and matrix metalloproteinase 9 as biomarkers of functional outcome following subarachnoid hemorrhage. Transl Stroke Res 2011;2:600-607. https://doi.org/10.1007/s12975-011-0117-x
- Shaul ME, Levy L, Sun J, Mishalian I, Singhal S, Kapoor V, Horng W, Fridlender G, Albelda SM, Fridlender ZG. Tumor-associated neutrophils display a distinct N1 profile following TGFβ modulation: a transcriptomics analysis of pro- vs. antitumor TANs. OncoImmunology 2016;5:e1232221.
- Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 2014;6:13.
- Ferreira da Mota NV, Brunialti MK, Santos SS, Machado FR, Assuncao M, Azevedo LC, Salomao R. Immunophenotyping of monocytes during human sepsis shows impairment in antigen presentation: a shift toward nonclassical differentiation and upregulation of FCγRi-receptor. Shock 2018;50:293-300. https://doi.org/10.1097/SHK.0000000000001078
- Gasco S, Zaragoza P, Garcia-Redondo A, Calvo AC, Osta R. Inflammatory and non-inflammatory monocytes as novel prognostic biomarkers of survival in SOD1G93A mouse model of Amyotrophic Lateral Sclerosis. PLoS One 2017;12:e0184626.
- Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol 2011;11:762-774. https://doi.org/10.1038/nri3070
- Burgess M, Wicks K, Gardasevic M, Mace KA. CX3CR1 expression identifies distinct macrophage populations that contribute differentially to inflammation and repair. Immunohorizons 2019;3:262-273. https://doi.org/10.4049/immunohorizons.1900038
- Ishida Y, Hayashi T, Goto T, Kimura A, Akimoto S, Mukaida N, Kondo T. Essential involvement of CX3CR1-mediated signals in the bactericidal host defense during septic peritonitis. J Immunol 2008;181:4208-4218. https://doi.org/10.4049/jimmunol.181.6.4208
- Nathan C. Metchnikoff 's legacy in 2008. Nat Immunol 2008;9:695-698. https://doi.org/10.1038/ni0708-695
- Kierdorf K, Prinz M, Geissmann F, Gomez Perdiguero E. Development and function of tissue resident macrophages in mice. Semin Immunol 2015;27:369-378. https://doi.org/10.1016/j.smim.2016.03.017
- Lavin Y, Mortha A, Rahman A, Merad M. Regulation of macrophage development and function in peripheral tissues. Nat Rev Immunol 2015;15:731-744. https://doi.org/10.1038/nri3920
- Epelman S, Lavine KJ, Randolph GJ. Origin and functions of tissue macrophages. Immunity 2014;41:21-35. https://doi.org/10.1016/j.immuni.2014.06.013
- Shaw TN, Houston SA, Wemyss K, Bridgeman HM, Barbera TA, Zangerle-Murray T, Strangward P, Ridley AJ, Wang P, Tamoutounour S, et al. Tissue-resident macrophages in the intestine are long lived and defined by TIM-4 and CD4 expression. J Exp Med 2018;215:1507-1518. https://doi.org/10.1084/jem.20180019
- Zhao Y, Zou W, Du J, Zhao Y. The origins and homeostasis of monocytes and tissue-resident macrophages in physiological situation. J Cell Physiol 2018;233:6425-6439. https://doi.org/10.1002/jcp.26461
- Loyher PL, Hamon P, Laviron M, Meghraoui-Kheddar A, Goncalves E, Deng Z, Torstensson S, Bercovici N, Baudesson de Chanville C, Combadiere B, et al. Macrophages of distinct origins contribute to tumor development in the lung. J Exp Med 2018;215:2536-2553. https://doi.org/10.1084/jem.20180534
- Poh AR, Ernst M. Targeting macrophages in cancer: from bench to bedside. Front Oncol 2018;8:49.
- Dixon LJ, Barnes M, Tang H, Pritchard MT, Nagy LE. Kupffer cells in the liver. Compr Physiol 2013;3:785-797. https://doi.org/10.1002/cphy.c120026
- Ju C, Reilly TP, Bourdi M, Radonovich MF, Brady JN, George JW, Pohl LR. Protective role of Kupffer cells in acetaminophen-induced hepatic injury in mice. Chem Res Toxicol 2002;15:1504-1513. https://doi.org/10.1021/tx0255976
- Nagy LE. Recent insights into the role of the innate immune system in the development of alcoholic liver disease. Exp Biol Med (Maywood) 2003;228:882-890. https://doi.org/10.1177/153537020322800803
- Hutchins NA, Wang F, Wang Y, Chung CS, Ayala A. Kupffer cells potentiate liver sinusoidal endothelial cell injury in sepsis by ligating programmed cell death ligand-1. J Leukoc Biol 2013;94:963-970. https://doi.org/10.1189/jlb.0113051
- Hutchins NA, Chung CS, Borgerding JN, Ayala CA, Ayala A. Kupffer cells protect liver sinusoidal endothelial cells from Fas-dependent apoptosis in sepsis by down-regulating gp130. Am J Pathol 2013;182:742-754. https://doi.org/10.1016/j.ajpath.2012.11.023
- Weinhard L, di Bartolomei G, Bolasco G, Machado P, Schieber NL, Neniskyte U, Exiga M, Vadisiute A, Raggioli A, Schertel A, et al. Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction. Nat Commun 2018;9:1228.
- Miyamoto A, Wake H, Ishikawa AW, Eto K, Shibata K, Murakoshi H, Koizumi S, Moorhouse AJ, Yoshimura Y, Nabekura J. Microglia contact induces synapse formation in developing somatosensory cortex. Nat Commun 2016;7:12540.
- Thion MS, Ginhoux F, Garel S. Microglia and early brain development: an intimate journey. Science 2018;362:185-189.
- Russo MV, McGavern DB. Immune surveillance of the CNS following infection and injury. Trends Immunol 2015;36:637-650. https://doi.org/10.1016/j.it.2015.08.002
- Hotchkiss RS, Coopersmith CM, McDunn JE, Ferguson TA. The sepsis seesaw: tilting toward immunosuppression. Nat Med 2009;15:496-497. https://doi.org/10.1038/nm0509-496
- Delano MJ, Ward PA. The immune system's role in sepsis progression, resolution, and long-term outcome. Immunol Rev 2016;274:330-353. https://doi.org/10.1111/imr.12499
- Fullerton JN, Gilroy DW. Resolution of inflammation: a new therapeutic frontier. Nat Rev Drug Discov 2016;15:551-567. https://doi.org/10.1038/nrd.2016.39
- Marino G, Niso-Santano M, Baehrecke EH, Kroemer G. Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol 2014;15:81-94. https://doi.org/10.1038/nrm3735
- Gump JM, Thorburn A. Autophagy and apoptosis: what is the connection? Trends Cell Biol 2011;21:387-392. https://doi.org/10.1016/j.tcb.2011.03.007
- Green DR, Oguin TH, Martinez J. The clearance of dying cells: table for two. Cell Death Differ 2016;23:915-926. https://doi.org/10.1038/cdd.2015.172
- Elliott MR, Koster KM, Murphy PS. Efferocytosis signaling in the regulation of macrophage inflammatory responses. J Immunol 2017;198:1387-1394. https://doi.org/10.4049/jimmunol.1601520
- Korns D, Frasch SC, Fernandez-Boyanapalli R, Henson PM, Bratton DL. Modulation of macrophage efferocytosis in inflammation. Front Immunol 2011;2:57.
- Needham DM, Davidson J, Cohen H, Hopkins RO, Weinert C, Wunsch H, Zawistowski C, BemisDougherty A, Berney SC, Bienvenu OJ, et al. Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders' conference. Crit Care Med 2012;40:502-509. https://doi.org/10.1097/CCM.0b013e318232da75
- Mehlhorn J, Freytag A, Schmidt K, Brunkhorst FM, Graf J, Troitzsch U, Schlattmann P, Wensing M, Gensichen J. Rehabilitation interventions for postintensive care syndrome: a systematic review. Crit Care Med 2014;42:1263-1271. https://doi.org/10.1097/CCM.0000000000000148
- Huang M, Parker AM, Bienvenu OJ, Dinglas VD, Colantuoni E, Hopkins RO, Needham DMNational Institutes of Health, National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Psychiatric symptoms in acute respiratory distress syndrome survivors: a 1-year national multicenter study. Crit Care Med 2016;44:954-965. https://doi.org/10.1097/CCM.0000000000001621
- Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 2010;304:1787-1794. https://doi.org/10.1001/jama.2010.1553
- Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, et al. Long-term cognitive impairment after critical illness. N Engl J Med 2013;369:1306-1316. https://doi.org/10.1056/NEJMoa1301372
- Greenhalgh AD, Zarruk JG, Healy LM, Baskar Jesudasan SJ, Jhelum P, Salmon CK, Formanek A, Russo MV, Antel JP, McGavern DB, et al. Peripherally derived macrophages modulate microglial function to reduce inflammation after CNS injury. PLoS Biol 2018;16:e2005264.
- Getts DR, Terry RL, Getts MT, Muller M, Rana S, Shrestha B, Radford J, Van Rooijen N, Campbell IL, King NJ. Ly6c+ "inflammatory monocytes" are microglial precursors recruited in a pathogenic manner in West Nile virus encephalitis. J Exp Med 2008;205:2319-2337. https://doi.org/10.1084/jem.20080421
- Shankar-Hari M, Rubenfeld GD. Understanding long-term outcomes following sepsis: implications and challenges. Curr Infect Dis Rep 2016;18:37.
- Sun A, Netzer G, Small DS, Hanish A, Fuchs BD, Gaieski DF, Mikkelsen ME. Association between index hospitalization and hospital readmission in sepsis survivors. Crit Care Med 2016;44:478-487. https://doi.org/10.1097/CCM.0000000000001464
- Jones TK, Fuchs BD, Small DS, Halpern SD, Hanish A, Umscheid CA, Baillie CA, Kerlin MP, Gaieski DF, Mikkelsen ME. Post-acute care use and hospital readmission after sepsis. Ann Am Thorac Soc 2015;12:904-913. https://doi.org/10.1513/AnnalsATS.201411-504OC
- Riche F, Chousterman BG, Valleur P, Mebazaa A, Launay JM, Gayat E. Protracted immune disorders at one year after ICU discharge in patients with septic shock. Crit Care 2018;22:42.
- Chan LC, Chaili S, Filler SG, Miller LS, Solis NV, Wang H, Johnson CW, Lee HK, Diaz LF, Yeaman MR. Innate immune memory contributes to host defense against recurrent skin and skin structure infections caused by methicillin-resistant staphylococcus aureus. Infect Immun 2017;85:e00876-16.
- Chang YH, Kumar R, Ng TH, Wang HC. What vaccination studies tell us about immunological memory within the innate immune system of cultured shrimp and crayfish. Dev Comp Immunol 2018;80:53-66. https://doi.org/10.1016/j.dci.2017.03.003
- Gourbal B, Pinaud S, Beckers GJ, Van Der Meer JW, Conrath U, Netea MG. Innate immune memory: an evolutionary perspective. Immunol Rev 2018;283:21-40. https://doi.org/10.1111/imr.12647
- Boraschi D, Italiani P. Innate immune memory: time for adopting a correct terminology. Front Immunol 2018;9:799.
- Foster SL, Hargreaves DC, Medzhitov R. Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 2007;447:972-978. https://doi.org/10.1038/nature05836
- Wendeln AC, Degenhardt K, Kaurani L, Gertig M, Ulas T, Jain G, Wagner J, Hasler LM, Wild K, Skodras A, et al. Innate immune memory in the brain shapes neurological disease hallmarks. Nature 2018;556:332-338. https://doi.org/10.1038/s41586-018-0023-4