Current challenges in understanding immune cell functions during septic syndromes

BMC Immunology

Matthew T Rondina²  McKenzie Carlisle¹  Zechariah Franks¹ 

[1] Program in Molecular Medicine, Salt Lake City 84112, , Utah, USA;Division of General Internal Medicine, University of Utah School of Medicine, Salt Lake City 84112, , Utah, USA

关键词: Immunity;    Inflammation;    Infection;    Dendritic cells;    Neutrophils;    Sepsis;   

Others  :  1149083
DOI  :  10.1186/s12865-015-0073-4

 received in 2014-10-07, accepted in 2015-02-05,  发布年份 2015

【 摘 要 】

Background

Sepsis is a dynamic infectious disease syndrome characterized by dysregulated inflammatory responses.

Results

Despite decades of research, improvements in the treatment of sepsis have been modest. These limited advances are likely due, in part, to multiple factors, including substantial heterogeneity in septic syndromes, significant knowledge gaps in our understanding of how immune cells function in sepsis, and limitations in animal models that accurately recapitulate the human septic milieu.The goal of this brief review is to describe current challenges in understanding immune cell functions during sepsis. We also provide a framework to guide scientists and clinicians in research and patient care as they strive to better understand dysregulated cell responses during sepsis.

Conclusions

Additional, well-designed translational studies in sepsis are critical for enhancing our understanding of the role of immune cells in sepsis.

【 授权许可】

   
2015 Franks et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 1.

【 参考文献 】

• [1]Kumar G, Kumar N, Taneja A, Kaleekal T, Tarima S, McGinley E et al.. Nationwide trends of severe sepsis in the 21st century (2000–2007). Chest. 2011; 140(5):1223-31.
• [2]Zimmerman JE, Kramer AA, Knaus WA. Changes in hospital mortality for United States intensive care unit admissions from 1988 to 2012. Crit Care. 2013; 17(2):R81. BioMed Central Full Text
• [3]Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J et al.. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med. 2010; 38(2):367-74.
• [4]Lagu T, Rothberg MB, Shieh MS, Pekow PS, Steingrub JS, Lindenauer PK. Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med. 2012; 40(3):754-61.
• [5]Angus DC, Carlet J, Brussels Roundtable P. Surviving intensive care: a report from the 2002 Brussels Roundtable. Intensive Care Med. 2003; 29(3):368-77.
• [6]Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001; 29(7):1303-10.
• [7]Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010; 304(16):1787-94.
• [8]Nasa P, Juneja D, Singh O, Dang R, Arora V. Severe sepsis and its impact on outcome in elderly and very elderly patients admitted in intensive care unit. J Intensive Care Med. 2012; 27(3):179-83.
• [9]Iwashyna TJ, Cooke CR, Wunsch H, Kahn JM. Population burden of long-term survivorship after severe sepsis in older Americans. J Am Geriatr Soc. 2012; 60(6):1070-7.
• [10]Angus DC. The search for effective therapy for sepsis: back to the drawing board? JAMA. 2011; 306(23):2614-5.
• [11]Cohen J, Opal S, Calandra T. Sepsis studies need new direction. Lancet Infect Dis. 2012; 12(7):503-5.
• [12]Harris ES, Rondina MT, Schwertz H, Weyrich AS, Zimmerman GA. Pathogenesis of Sepsis and Sepsis-Induced Acute Lung Injury. In: Acute Respiratory Distress Syndrome. Choi AMK, editor. Informa Healthcare, USA; 2010: p.369-419.
• [13]Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013; 13(12):862-74.
• [14]Martin GS, Mannino DM, Moss M. The effect of age on the development and outcome of adult sepsis. Crit Care Med. 2006; 34(1):15-21.
• [15]Miller RA. The aging immune system: primer and prospectus. Science. 1996; 273(5271):70-4.
• [16]Pawelec G. Immunosenescence: impact in the young as well as the old? Mech Ageing Dev. 1999; 108(1):1-7.
• [17]Weiskopf D, Weinberger B, Grubeck-Loebenstein B. The aging of the immune system. Transpl Int. 2009; 22(11):1041-50.
• [18]Rondina MT, Fraughton T, Brown SM, Carlisle M, Miller RR, 3rd, Harris ES, Zimmerman GA, Weyrich AS, Grissom CK: Enhanced Platelet-Monocyte Aggregation in Older Patients Correlates with Increased 28-Day Mortality Risk Following Severe Sepsis and Septic Shock. Journal of Gerontology: Medical Sciences 2014, In press.
• [19]Mohebali D, Kaplan D, Carlisle M, Supiano MA, Rondina MT. Alterations in platelet function during aging: clinical correlations with thromboinflammatory disease in older adults. J Am Geriatr Soc. 2014; 62(3):529-35.
• [20]Martin G, Brunkhorst FM, Janes JM, Reinhart K, Sundin DP, Garnett K et al.. The international PROGRESS registry of patients with severe sepsis: drotrecogin alfa (activated) use and patient outcomes. Crit Care. 2009; 13(3):R103. BioMed Central Full Text
• [21]Danai PA, Moss M, Mannino DM, Martin GS. The epidemiology of sepsis in patients with malignancy. Chest. 2006; 129(6):1432-40.
• [22]Prescott HC, Chang VW, O’Brien JM, Langa KM, Iwashyna TJ. Obesity and 1-year outcomes in older Americans with severe sepsis. Crit Care Med. 2014; 42(8):1766-74.
• [23]Sorensen TI, Nielsen GG, Andersen PK, Teasdale TW. Genetic and environmental influences on premature death in adult adoptees. N Engl J Med. 1988; 318(12):727-32.
• [24]Wurfel MM. Genetic insights into sepsis: what have we learned and how will it help? Curr Pharm Des. 2008; 14(19):1900-11.
• [25]Petersen L, Nielsen GG, Andersen PK, Sorensen TI. Case–control study of genetic and environmental influences on premature death of adult adoptees. Genet Epidemiol. 2002; 23(2):123-32.
• [26]Tang BM, Huang SJ, McLean AS. Genome-wide transcription profiling of human sepsis: a systematic review. Crit Care. 2010; 14(6):R237. BioMed Central Full Text
• [27]Giroir BP, Johnson JH, Brown T, Allen GL, Beutler B. The tissue distribution of tumor necrosis factor biosynthesis during endotoxemia. J Clin Invest. 1992; 90(3):693-8.
• [28]Laszik Z, Nadasdy T, Johnson LD, Lerner MR, Brackett D, Silva FG. Renal interleukin-1 expression during endotoxemia and gram-negative septicemia in conscious rats. Circ Shock. 1994; 43(3):115-21.
• [29]Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013; 369(9):840-51.
• [30]Bone RC, Grodzin CJ, Balk RA. Sepsis: a new hypothesis for pathogenesis of the disease process. Chest. 1997; 112(1):235-43.
• [31]Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH et al.. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011; 306(23):2594-605.
• [32]Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM et al.. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med. 1999; 27(7):1230-51.
• [33]Latifi SQ, O’Riordan MA, Levine AD. Interleukin-10 controls the onset of irreversible septic shock. Infect Immun. 2002; 70(8):4441-6.
• [34]Tschoeke SK, Oberholzer C, LaFace D, Hutchins B, Moldawer LL, Oberholzer A. Endogenous IL-10 regulates sepsis-induced thymic apoptosis and improves survival in septic IL-10 null mice. Scand J Immunol. 2008; 68(6):565-71.
• [35]Derive M, Bouazza Y, Alauzet C, Gibot S. Myeloid-derived suppressor cells control microbial sepsis. Intensive Care Med. 2012; 38(6):1040-9.
• [36]Munford RS, Pugin J. Normal responses to injury prevent systemic inflammation and can be immunosuppressive. Am J Respir Crit Care Med. 2001; 163(2):316-21.
• [37]Faix JD. Biomarkers of sepsis. Crit Rev Clin Lab Sci. 2013; 50(1):23-36.
• [38]Stearns-Kurosawa DJ, Osuchowski MF, Valentine C, Kurosawa S, Remick DG. The pathogenesis of sepsis. Annu Rev Pathol. 2011; 6:19-48.
• [39]Kovach MA, Standiford TJ. The function of neutrophils in sepsis. Curr Opin Infect Dis. 2012; 25(3):321-7.
• [40]Cohen J. The immunopathogenesis of sepsis. Nature. 2002; 420(6917):885-91.
• [41]Biswas SK, Lopez-Collazo E. Endotoxin tolerance: new mechanisms, molecules and clinical significance. Trends Immunol. 2009; 30(10):475-87.
• [42]Souza-Fonseca-Guimaraes F, Adib-Conquy M, Cavaillon JM. Natural killer (NK) cells in antibacterial innate immunity: angels or devils? Mol Med. 2012; 18:270-85.
• [43]Tamayo E, Gomez E, Bustamante J, Gomez-Herreras JI, Fonteriz R, Bobillo F et al.. Evolution of neutrophil apoptosis in septic shock survivors and nonsurvivors. J Crit Care. 2012; 27(4):415. e411-411
• [44]Alves-Filho JC, Spiller F, Cunha FQ. Neutrophil paralysis in sepsis. Shock. 2010; 34 Suppl 1:15-21.
• [45]Muller Kobold AC, Tulleken JE, Zijlstra JG, Sluiter W, Hermans J, Kallenberg CG et al.. Leukocyte activation in sepsis; correlations with disease state and mortality. Intensive Care Med. 2000; 26(7):883-92.
• [46]Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 2011; 11(8):519-31.
• [47]McInturff AM, Cody MJ, Elliott EA, Glenn JW, Rowley JW, Rondina MT et al.. Mammalian target of rapamycin regulates neutrophil extracellular trap formation via induction of hypoxia-inducible factor 1 alpha. Blood. 2012; 120(15):3118-25.
• [48]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(4):463-9.
• [49]Kraemer BF, Campbell RA, Schwertz H, Cody MJ, Franks Z, Tolley ND et al.. Novel anti-bacterial activities of beta-defensin 1 in human platelets: suppression of pathogen growth and signaling of neutrophil extracellular trap formation. PLoS Pathog. 2011; 7(11):e1002355.
• [50]Yost CC, Cody MJ, Harris ES, Thornton NL, McInturff AM, Martinez ML et al.. Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates. Blood. 2009; 113(25):6419-27.
• [51]Villanueva E, Yalavarthi S, Berthier CC, Hodgin JB, Khandpur R, Lin AM et al.. Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus. J Immunol. 2011; 187(1):538-52.
• [52]Martinod K, Wagner DD. Thrombosis: tangled up in NETs. Blood. 2014; 123(18):2768-76.
• [53]Yipp BG, Kubes P. NETosis: how vital is it? Blood. 2013; 122(16):2784-94.
• [54]Xu J, Zhang X, Pelayo R, Monestier M, Ammollo CT, Semeraro F et al.. Extracellular histones are major mediators of death in sepsis. Nat Med. 2009; 15(11):1318-21.
• [55]Hotchkiss RS, Tinsley KW, Swanson PE, Grayson MH, Osborne DF, Wagner TH et al.. Depletion of dendritic cells, but not macrophages, in patients with sepsis. J Immunol. 2002; 168(5):2493-500.
• [56]Gautier EL, Huby T, Saint-Charles F, Ouzilleau B, Chapman MJ, Lesnik P. Enhanced dendritic cell survival attenuates lipopolysaccharide-induced immunosuppression and increases resistance to lethal endotoxic shock. J Immunol. 2008; 180(10):6941-6.
• [57]Benjamim CF, Lundy SK, Lukacs NW, Hogaboam CM, Kunkel SL. Reversal of long-term sepsis-induced immunosuppression by dendritic cells. Blood. 2005; 105(9):3588-95.
• [58]Venet F, Chung CS, Kherouf H, Geeraert A, Malcus C, Poitevin F et al.. Increased circulating regulatory T cells (CD4(+)CD25 (+)CD127 (−)) contribute to lymphocyte anergy in septic shock patients. Intensive Care Med. 2009; 35(4):678-86.
• [59]Venet F, Pachot A, Debard AL, Bohe J, Bienvenu J, Lepape A et al.. Increased percentage of CD4 + CD25+ regulatory T cells during septic shock is due to the decrease of CD4 + CD25- lymphocytes. Crit Care Med. 2004; 32(11):2329-31.
• [60]Venet F, Pachot A, Debard AL, Bohe J, Bienvenu J, Lepape A et al.. Human CD4 + CD25+ regulatory T lymphocytes inhibit lipopolysaccharide-induced monocyte survival through a Fas/Fas ligand-dependent mechanism. J Immunol. 2006; 177(9):6540-7.
• [61]Dyson A, Singer M. Animal models of sepsis: why does preclinical efficacy fail to translate to the clinical setting? Crit Care Med. 2009; 37(1 Suppl):S30-7.
• [62]Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A. 2013;110(9):3507–12
• [63]Xiao W, Mindrinos MN, Seok J, Cuschieri J, Cuenca AG, Gao H, et al. A genomic storm in critically injured humans. J Exp Med. 2011;208(13):2581–90.
• [64]Takao K, Miyakawa T. Genomic responses in mouse models greatly mimic human inflammatory diseases. Proc Natl Acad Sci U S A. 2015;112(4):1167–72.
• [65]Dejager L, Pinheiro I, Dejonckheere E, Libert C. Cecal ligation and puncture: the gold standard model for polymicrobial sepsis? Trends Microbiol. 2011; 19(4):198-208.
• [66]Chang KC, Unsinger J, Davis CG, Schwulst SJ, Muenzer JT, Strasser A et al.. Multiple triggers of cell death in sepsis: death receptor and mitochondrial-mediated apoptosis. FASEB J. 2007; 21(3):708-19.