New immune targets to improve survival from sepsis

References for ‘New immune targets to improve survival from sepsis’, in Drug Target Review Issue 2 2022.


  1. Sepsis | CDC. Accessed May 10, 2022.
  2. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101(6):1644-1655. doi:10.1378/chest.101.6.1644
  3. Minasyan H. Sepsis: mechanisms of bacterial injury to the patient. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2019;27(1). doi:10.1186/S13049-019-0596-4
  4. Venet F, Monneret G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nature Reviews Nephrology. 2018;14(2):121-137. doi:10.1038/nrneph.2017.165
  5. Pierrakos C, Vincent J louis. Sepsis biomarkers : a review. Critical Care. 2010;14:1-18.
  6. Rudiger A, Singer M. Mechanisms of sepsis-induced cardiac dysfunction. Critical Care Medicine. 2007;35(6):1599-1608. doi:10.1097/01.CCM.0000266683.64081.02
  7. Poveda-Jaramillo R. Heart Dysfunction in Sepsis. J Cardiothorac Vasc Anesth. 2021;35(1):298-309. doi:10.1053/J.JVCA.2020.07.026
  8. David S, Kümpers P, van Slyke P, Parikh SM. Mending leaky blood vessels: the angiopoietin-Tie2 pathway in sepsis. J Pharmacol Exp Ther. 2013;345(1):2-6. doi:10.1124/JPET.112.201061
  9. Gu M, Mei XL, Zhao YN. Sepsis and Cerebral Dysfunction: BBB Damage, Neuroinflammation, Oxidative Stress, Apoptosis and Autophagy as Key Mediators and the Potential Therapeutic Approaches. Neurotox Res. 2021;39(2):489-503. doi:10.1007/S12640-020-00270-5
  10. Schultze JL, Mass E, Schlitzer A. Emerging Principles in Myelopoiesis at Homeostasis and during Infection and Inflammation. Immunity. 2019;50(2):288-301. doi:10.1016/j.immuni.2019.01.019
  11. MacNamara KC, Oduro K, Martin O, et al. Infection-Induced Myelopoiesis during Intracellular Bacterial Infection Is Critically Dependent upon IFN-γ Signaling. The Journal of Immunology. 2011;186(2):1032-1043. doi:10.4049/jimmunol.1001893
  12. Chapple RH, Tseng YJ, Hu T, et al. Lineage tracing of murine adult hematopoietic stem cells reveals active contribution to steady-state hematopoiesis. Blood Advances. 2018;2(11):1220-1228. doi:10.1182/bloodadvances.2018016295
  13. Morales-Mantilla DE, King KY. The Role of Interferon-Gamma in Hematopoietic Stem Cell Development , Homeostasis , and Disease. Current Stem Cell Reports. 2018;4(3):264-271. doi:10.1007/s40778-018-0139-3
  14. Morales-Mantilla DE, Kain B, Le D, Flores AR, Paust S, King KY. Hematopoietic stem and progenitor cells improve survival from sepsis by boosting immunomodulatory cells. Elife. 2022;11:1-20. doi:10.7554/ELIFE.74561
  15. Matatall KA, Jeong M, Chen S, et al. Chronic Infection Depletes Hematopoietic Stem Cells through Stress-Induced Terminal Differentiation. Cell Reports. 2016;17(10):2584-2595. doi:10.1016/j.celrep.2016.11.031
  16. Pietras EM, Mirantes-Barbeito C, Fong S, et al. Chronic interleukin-1 exposure drives haematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal. Nature Cell Biology. 2016;18(6):607-618. doi:10.1038/ncb3346
  17. Libregts SF, Gutiérrez L, de Bruin AM, et al. Chronic IFN-γ production in mice induces anemia by reducing erythrocyte life span and inhibiting erythropoiesis through an IRF-1 / PU . 1 axis. Blood. 2011;118(9):2578-2588. doi:10.1182/blood-2010-10-315218
  18. Bode D, Cull AH, Rubio-Lara JA, Kent DG. Exploiting Single-Cell Tools in Gene and Cell Therapy. Front Immunol. 2021;12. doi:10.3389/FIMMU.2021.702636
  19. Campbell A, Brieva T, Raviv L, et al. Concise Review: Process Development Considerations for Cell Therapy. Stem Cells Transl Med. 2015;4(10):1155-1163. doi:10.5966/SCTM.2014-0294
  20. Buzhor E, Leshansky L, Blumenthal J, et al. Cell-based therapy approaches: the hope for incurable diseases. Regenerative Med. 2014;9(5):649-672. doi:10.2217/RME.14.35
  21. Gu BJ, Kung DK, Chen HCI. Cell Therapy for Stroke: A Mechanistic Analysis. Neurosurgery. 2021;88(4):733-745. doi:10.1093/NEUROS/NYAA531
  22. El-Badawy A, El-Badri N. Clinical Efficacy of Stem Cell Therapy for Diabetes Mellitus: A Meta-Analysis. PLoS One. 2016;11(4). doi:10.1371/JOURNAL.PONE.0151938
  23. Wang Z, Cao YJ. Adoptive Cell Therapy Targeting Neoantigens: A Frontier for Cancer Research. Front Immunol. 2020;11. doi:10.3389/FIMMU.2020.00176
  24. Schrijver IT, Théroude C, Roger T. Myeloid derived suppressor cells in sepsis. Frontiers in Immunology. 2019;10:1-10. doi:10.3389/fimmu.2019.00327
  25. Delano MJ, Scumpia PO, Weinstein JS, et al. MyD88-dependent expansion of an immature GR-1 +CD11b+ population induces T cell suppression and Th2 polarization in sepsis. Journal of Experimental Medicine. 2007;204(6):1463-1474. doi:10.1084/jem.20062602
  26. Uhel F, Azzaoui I, Grégoire M, et al. Early expansion of circulating granulocytic myeloid-derived suppressor cells predicts development of nosocomial infections in patients with sepsis. American Journal of Respiratory and Critical Care Medicine. 2017;196(3):315-327. doi:10.1164/rccm.201606-1143OC
  27. Köstlin N, Vogelmann M, Spring B, et al. Granulocytic myeloid-derived suppressor cells from human cord blood modulate T-helper cell response towards an anti-inflammatory phenotype. Immunology. 2017;152:89-101. doi:10.1111/imm.12751
  28. Jaffer U, Wade RG, Gourlay T. Cytokines in the systemic inflammatory response syndrome: a review. HSR Proceedings. 2010;2:161-175.
  29. Huang KJ, Su IJ, Theron M, et al. An interferon-γ-related cytokine storm in SARS patients. Journal of Medical Virology. 2005;75(2):185-194. doi:10.1002/jmv.20255
  30. Baldridge MT, King KY, Boles NC, Weksberg DC, Goodell MA. Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection. Nature. 2010;465:793-797. doi:10.1038/nature09135
  31. Essers MAG, Offner S, Blanco-Bose WE, et al. IFNα activates dormant haematopoietic stem cells in vivo. Nature. 2009;458:904-908. doi:10.1038/nature07815
  32. Matatall KA, Shen CC, Challen GA, King KY. Type II interferon promotes differentiation of myeloid-biased hematopoietic stem cells. Stem Cells. 2014;32(11):3023-3030. doi:10.1002/stem.1799
  33. Schürch CM, Riether C, Ochsenbein AF. Cytotoxic CD8+ T cells stimulate hematopoietic progenitors by promoting cytokine release from bone marrow mesenchymal stromal cells. Cell Stem Cell. 2014;14(4):460-472. doi:10.1016/j.stem.2014.01.002
  34. Esplin BL, Shimazu T, Welner RS, et al. Chronic Exposure to a TLR Ligand Injures Hematopoietic Stem Cells. The Journal of Immunology. 2011;186(9):5367-5375. doi:10.4049/jimmunol.1003438
  35. Pietras EM, Lakshminarasimhan R, Techner JM, et al. Re-entry into quiescence protects hematopoietic stem cells from the killing effect of chronic exposure to type I interferons. The Journal of Experimental Medicine. 2014;211(2):245-262. doi:10.1084/jem.20131043
  36. Takizawa H, Fritsch K, Kovtonyuk L V., et al. Pathogen-Induced TLR4-TRIF Innate Immune Signaling in Hematopoietic Stem Cells Promotes Proliferation but Reduces Competitive Fitness. Cell Stem Cell. 2017;21(2):225-240.e5. doi:10.1016/j.stem.2017.06.013
  37. Chen CI, Zhang L, Datta SK. Hematopoietic stem and multipotent progenitor cells produce IL-17, IL-21 and other cytokines in response to TLR signals associated with late apoptotic products and augment memory Th17 and Tc17 cells in the bone marrow of normal and lupus mice. Clinical Immunology. 2016;162:9-26. doi:10.1016/j.clim.2015.10.007
  38. Baldridge MT, King KY, Goodell MA. Inflammatory signals regulate hematopoietic stem cells. Trends in Immunology. 2011;32(2):57-65. doi:10.1016/
  39. King KY, Baldridge MT, Weksberg DC, et al. Irgm1 protects hematopoietic stem cells by negative regulation of interferon signaling. Blood. 2011;118(6):1525-1533. doi:10.1182/blood-2011-01-328682
  40. King KY, Goodell MA. Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response. Nature Reviews Immunology. 2011;11(10):685-692. doi:10.1038/nri3062
  41. Kaufmann E, Sanz J, Dunn JL, et al. BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis. Cell. 2018;172(1-2):176-182.e19. doi:10.1016/j.cell.2017.12.031
  42. Klein K, Castillo B. Historical perspectives, current status, and ethical issues in granulocyte transfusion. Annals of Clinical and Laboratory Science. 2017;47(4):501-507.
  43. Estcourt LJ, Stanworth S, Doree C, et al. Granulocyte transfusions for preventing infections in people with neutropenia or neutrophil dysfunction. Cochrane Database of Systematic Reviews. 2016;2016(4). doi:10.1002/14651858.CD005339.pub2
  44. Robinson SP, Marks DI. Granulocyte transfusions in the G-CSF era. Where do we stand? Bone Marrow Transplantation. Published online 2004. doi:10.1038/sj.bmt.1704630
  45. Teofili L, Valentini CG, di Blasi R, et al. Dose-dependent effect of granulocyte transfusions in hematological patients with febrile neutropenia. PLoS ONE. 2016;11(8):1-15. doi:10.1371/journal.pone.0159569
  46. Price TH, Boeckh M, Harrison RW, et al. Efficacy of transfusion with granulocytes from G-CSF / dexamethasone – treated donors in neutropenic patients with infection. Blood. 2015;126(18):2153-2162. doi:10.1182/blood-2015-05-645986.Presented
  47. Estcourt L, Stanworth S, Hopewell S, Doree C, Trivella M, Massey E. Cochrane Database of Systematic Reviews Granulocyte transfusions for treating infections in people with neutropenia or neutrophil dysfunction (Review). Cochrane Database of Systematic Reviews. 2016;(4). doi:10.1002/14651858.CD005339.pub2
  48. Hidalgo A, Chilvers ER, Summers C, Koenderman L. The Neutrophil Life Cycle. Trends in Immunology. 2019;40(7). doi:10.1016/
  49. Pietras EM, Reynaud D, Kang YA, et al. Functionally Distinct Subsets of Lineage-Biased Multipotent Progenitors Control Blood Production in Normal and Regenerative Conditions. Cell Stem Cell. 2015;17(1):35-46. doi:10.1016/j.stem.2015.05.003
  50. Cordeiro Gomes A, Hara T, Lim VY, et al. Hematopoietic Stem Cell Niches Produce Lineage-Instructive Signals to Control Multipotent Progenitor Differentiation. Immunity. 2016;45(6):1219-1231. doi:10.1016/j.immuni.2016.11.004
  51. Joyce D, Fujino M, Morita M, et al. Induced pluripotent stem cells-derived myeloid-derived suppressor cells regulate the CD8 + T cell response. Stem Cell Res. 2018;29:32-41. doi:10.1016/J.SCR.2018.03.009

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.