An IL-10/DEL-1 axis supports granulopoiesis and survival from sepsis in early life.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 Jan 2024
23 Jan 2024
Historique:
received:
24
10
2021
accepted:
03
12
2023
medline:
24
1
2024
pubmed:
24
1
2024
entrez:
23
1
2024
Statut:
epublish
Résumé
The limited reserves of neutrophils are implicated in the susceptibility to infection in neonates, however the regulation of neutrophil kinetics in infections in early life remains poorly understood. Here we show that the developmental endothelial locus (DEL-1) is elevated in neonates and is critical for survival from neonatal polymicrobial sepsis, by supporting emergency granulopoiesis. Septic DEL-1 deficient neonate mice display low numbers of myeloid-biased multipotent and granulocyte-macrophage progenitors in the bone marrow, resulting in neutropenia, exaggerated bacteremia, and increased mortality; defects that are rescued by DEL-1 administration. A high IL-10/IL-17A ratio, observed in newborn sepsis, sustains tissue DEL-1 expression, as IL-10 upregulates while IL-17 downregulates DEL-1. Consistently, serum DEL-1 and blood neutrophils are elevated in septic adult and neonate patients with high serum IL-10/IL-17A ratio, and mortality is lower in septic patients with high serum DEL-1. Therefore, IL-10/DEL-1 axis supports emergency granulopoiesis, prevents neutropenia and promotes sepsis survival in early life.
Identifiants
pubmed: 38263289
doi: 10.1038/s41467-023-44178-y
pii: 10.1038/s41467-023-44178-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
680Informations de copyright
© 2024. The Author(s).
Références
Gaieski, D. F. et al. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit. Care Med. 41, 1167–1174 (2013).
pubmed: 23442987
doi: 10.1097/CCM.0b013e31827c09f8
Camacho-Gonzalez, A. et al. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr. Clin. North Am. 60, 367–389 (2013).
pubmed: 23481106
pmcid: 4405627
doi: 10.1016/j.pcl.2012.12.003
Vergadi, E. et al. Changes in the incidence and epidemiology of neonatal group B Streptococcal disease over the last two decades in Crete, Greece. Infect. Dis. Rep. 10, 7744 (2018).
pubmed: 30662690
pmcid: 6315311
doi: 10.4081/idr.2018.7744
Levy, O. Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat. Rev. Immunol. 7, 379–390 (2007).
pubmed: 17457344
doi: 10.1038/nri2075
Angelone, D. F. et al. Innate immunity of the human newborn is polarized toward a high ratio of IL-6/TNF-alpha production in vitro and in vivo. Pediatr. Res. 60, 205–209 (2006).
pubmed: 16864705
doi: 10.1203/01.pdr.0000228319.10481.ea
Stearns-Kurosawa, D. J. et al. The pathogenesis of sepsis. Annu. Rev. Pathol. 6, 19–48 (2011).
pubmed: 20887193
pmcid: 3684427
doi: 10.1146/annurev-pathol-011110-130327
Wynn, J. L. et al. Defective innate immunity predisposes murine neonates to poor sepsis outcome but is reversed by TLR agonists. Blood. 112, 1750–1758 (2008).
pubmed: 18591384
pmcid: 2518883
doi: 10.1182/blood-2008-01-130500
Chavakis, E. et al. Novel aspects in the regulation of the leukocyte adhesion cascade. Thromb. Haemost. 102, 191–197 (2009).
pubmed: 19652868
pmcid: 2722029
doi: 10.1160/TH08-12-0844
Kovach, M. A. et al. The function of neutrophils in sepsis. Curr. Opin. Infect. Dis. 25, 321–327 (2012).
pubmed: 22421753
doi: 10.1097/QCO.0b013e3283528c9b
Buschmann, K. et al. RAGE controls leukocyte adhesion in preterm and term infants. BMC Immunol. 15, 53 (2014).
pubmed: 25428166
pmcid: 4256735
doi: 10.1186/s12865-014-0053-0
Bracho, F. et al. Potential use of granulocyte colon-stimulating factor and granulocyte-macrophage colony-stimulating factor in neonates. Curr. Opin. Hematol. 5, 215–220 (1998).
pubmed: 9664163
doi: 10.1097/00062752-199805000-00012
Cuenca, A. G. et al. Delayed emergency myelopoiesis following polymicrobial sepsis in neonates. Innate Immun. 21, 386–391 (2015).
pubmed: 25106654
doi: 10.1177/1753425914542445
Hajishengallis, G. et al. DEL-1-regulated immune plasticity and inflammatory disorders. Trends Mol. Med. 25, 444–459 (2019).
pubmed: 30885428
pmcid: 6488420
doi: 10.1016/j.molmed.2019.02.010
Choi, E. Y. et al. Del-1, an endogenous leukocyte-endothelial adhesion inhibitor, limits inflammatory cell recruitment. Science 322, 1101–1104 (2008).
pubmed: 19008446
pmcid: 2753175
doi: 10.1126/science.1165218
Hajishengallis, G. et al. Endogenous modulators of inflammatory cell recruitment. Trends Immunol. 34, 1–6 (2013).
pubmed: 22951309
doi: 10.1016/j.it.2012.08.003
Schurpf, T. et al. The RGD finger of Del-1 is a unique structural feature critical for integrin binding. FASEB J. 26, 3412–3420 (2012).
pubmed: 22601780
pmcid: 3405271
doi: 10.1096/fj.11-202036
Vestweber, D. Adhesion and signaling molecules controlling the transmigration of leukocytes through endothelium. Immunol. Rev. 218, 178–196 (2007).
pubmed: 17624953
doi: 10.1111/j.1600-065X.2007.00533.x
Kourtzelis, I. et al. DEL-1 promotes macrophage efferocytosis and clearance of inflammation. Nat. Immunol. 20, 40–49 (2019).
pubmed: 30455459
doi: 10.1038/s41590-018-0249-1
Li, X. et al. The DEL-1/beta3 integrin axis promotes regulatory T cell responses during inflammation resolution. J. Clin. Investig. 130, 6261–6277 (2020).
pubmed: 32817592
pmcid: 7685741
doi: 10.1172/JCI137530
Eskan, M. A. et al. The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss. Nat. Immunol. 13, 465–473 (2012).
pubmed: 22447028
pmcid: 3330141
doi: 10.1038/ni.2260
Choi, E. Y. et al. Developmental endothelial locus-1 is a homeostatic factor in the central nervous system limiting neuroinflammation and demyelination. Mol. Psychiatry 20, 880–888 (2015).
pubmed: 25385367
doi: 10.1038/mp.2014.146
Shin, J. et al. DEL-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in nonhuman primates. Sci. Transl. Med. 7, 307ra155 (2015).
pubmed: 26424570
pmcid: 4593066
doi: 10.1126/scitranslmed.aac5380
Mitroulis, I. et al. Secreted protein Del-1 regulates myelopoiesis in the hematopoietic stem cell niche. J. Clin. Investig. 127, 3624–3639 (2017).
pubmed: 28846069
pmcid: 5617665
doi: 10.1172/JCI92571
Shin, J. et al. Expression and function of the homeostatic molecule Del-1 in endothelial cells and the periodontal tissue. Clin. Dev. Immunol. 2013, 617809 (2013).
pubmed: 24416060
pmcid: 3876683
doi: 10.1155/2013/617809
Kanczkowski, W. et al. Role of the endothelial-derived endogenous anti-inflammatory factor Del-1 in inflammation-mediated adrenal gland dysfunction. Endocrinology 154, 1181–1189 (2013).
pubmed: 23364949
doi: 10.1210/en.2012-1617
Kang, Y. Y. et al. Deficiency of developmental endothelial locus-1 (Del-1) aggravates bleomycin-induced pulmonary fibrosis in mice. Biochem. Biophys. Res. Commun. 445, 369–374 (2014).
pubmed: 24525119
doi: 10.1016/j.bbrc.2014.02.009
Wynn, J. L. et al. Increased mortality and altered immunity in neonatal sepsis produced by generalized peritonitis. Shock 28, 675–683 (2007).
pubmed: 17621256
doi: 10.1097/shk.0b013e3180556d09
Levy, O. Impaired innate immunity at birth: deficiency of bactericidal/permeability-increasing protein (BPI) in the neutrophils of newborns. Pediatr. Res. 51, 667–669 (2002).
pubmed: 12032258
doi: 10.1203/00006450-200206000-00001
Drossou, V. et al. Concentrations of main serum opsonins in early infancy. Arch. Dis. Child Fetal Neonatal Ed. 72, F172–F175 (1995).
pubmed: 7796232
pmcid: 2528447
doi: 10.1136/fn.72.3.F172
Conly, M. E. & Speert, D. P. Human neonatal monocyte-derived macrophages and neutrophils exhibit normal nonopsonic and opsonic receptor-mediated phagocytosis and superoxide anion production. Biol Neonate. 60, 361–366 (1991).
pubmed: 1665710
doi: 10.1159/000243433
Gille, C. H. et al. Phagocytosis and postphagocytic reaction of cord blood and adult blood monocyte after infection with green fluorescent protein-labeled Escherichia coli and group B Streptococci. Cytometry B Clin. Cytom. 76, 271–284 (2009).
pubmed: 19288547
doi: 10.1002/cyto.b.20474
Suratt, B. T. et al. Role of the CXCR4/SDF-1 chemokine axis in circulating neutrophil homeostasis. Blood. 104, 565–571 (2004).
pubmed: 15054039
doi: 10.1182/blood-2003-10-3638
Mitroulis, I. et al. Modulation of myelopoiesis progenitors is an integral component of trained immunity. Cell 172, 147–161.e12 (2018).
pubmed: 29328910
pmcid: 5766828
doi: 10.1016/j.cell.2017.11.034
Barman, P. K. & Goodridge, H. S. Microbial sensing by hematopoietic stem and progenitor cells. Stem Cells 40, 14–21 (2022).
pubmed: 35511863
pmcid: 9072977
doi: 10.1093/stmcls/sxab007
Pietras, E. M. et al. Functionally distinct subsets of lineage-biased multipotent progenitors control blood production in normal and regenerative conditions. Cell Stem Cell. 17, 35–46 (2015).
pubmed: 26095048
pmcid: 4542150
doi: 10.1016/j.stem.2015.05.003
Chavakis, T. et al. Inflammatory modulation of hematopoiesis: linking trained immunity and clonal hematopoiesis with chronic disorders. Annu. Rev. Physiol. 84, 183–207 (2022).
pubmed: 34614373
doi: 10.1146/annurev-physiol-052521-013627
Köhler, A. et al. G-CSF-mediated thrombopoietin release triggers neutrophil motility and mobilization from bone marrow via induction of Cxcr2 ligands. Blood 117, 4349–4357 (2011).
pubmed: 21224471
pmcid: 3087483
doi: 10.1182/blood-2010-09-308387
Maekawa, T. et al. Antagonistic effects of IL-17 and D-resolvins on endothelial Del-1 expression through a GSK-3beta-C/EBPbeta pathway. Nat. Commun. 6, 8272 (2015).
pubmed: 26374165
doi: 10.1038/ncomms9272
Ziogas, A. et al. DHEA inhibits leukocyte recruitment through regulation of the integrin antagonist DEL-1. J. Immunol. 204, 1214–1224 (2020).
pubmed: 31980574
pmcid: 7026770
doi: 10.4049/jimmunol.1900746
Li, M., Zhong, D. & Li, G. Regulatory role of local tissue signal Del-1 in cancer and inflammation: a review. Cell Mol. Biol. Lett. 26, 31 (2021).
pubmed: 34217213
pmcid: 8254313
doi: 10.1186/s11658-021-00274-9
Wang, H. et al. Stromal cell-derived DEL-1 inhibits Tfh cell activation and inflammatory arthritis. J. Clin. Investig. 1, 131:e150578 (2021).
Kim, W. Y. et al. Serum developmental endothelial locus-1 is associated with severity of sepsis in animals and humans. Sci. Rep. 9, 13005 (2019).
pubmed: 31506547
pmcid: 6737092
doi: 10.1038/s41598-019-49564-5
Sperandio, M. et al. Ontogenetic regulation of leukocyte recruitment in mouse yolk sac vessels. Blood 121, e118–e128 (2013).
pubmed: 23525796
pmcid: 3713423
doi: 10.1182/blood-2012-07-447144
Nussbaum, C. et al. Neutrophil and endothelial adhesive function during human fetal ontogeny. J. Leukoc. Biol. 93, 175–184 (2013).
pubmed: 23233729
pmcid: 4050519
doi: 10.1189/jlb.0912468
Basha, S. et al. Immune responses in neonates. Expert Rev. Clin. Immunol. 10, 1171–1184 (2014).
pubmed: 25088080
pmcid: 4407563
doi: 10.1586/1744666X.2014.942288
Rebuck, N. et al. Neutrophil adhesion molecules in term and premature infants: normal or enhanced leucocyte integrins but defective L-selectin expression and shedding. Clin. Exp. Immunol. 101, 183–189 (1995).
pubmed: 7542575
pmcid: 1553291
doi: 10.1111/j.1365-2249.1995.tb02296.x
Hidalgo, A. et al. Enforced fucosylation of neonatal CD34+ cells generates selectin ligands that enhance the initial interactions with microvessels but not homing to bone marrow. Blood. 105, 567–575 (2005).
pubmed: 15367439
doi: 10.1182/blood-2004-03-1026
van Griensven, M. et al. Leukocyte-endothelial interactions via ICAM-1 are detrimental in polymicrobial sepsis. Shock 25, 254–259 (2006).
pubmed: 16552357
doi: 10.1097/01.shk.0000196497.49683.13
Phillipson, M. et al. The neutrophil in vascular inflammation. Nat. Med. 17, 1381–1390 (2011).
pubmed: 22064428
pmcid: 7095830
doi: 10.1038/nm.2514
Vergadi, E. et al. Akt2 deficiency protects from acute lung injury via alternative macrophage activation and miR-146a induction in mice. J. Immunol. 192, 394–406 (2014).
pubmed: 24277697
doi: 10.4049/jimmunol.1300959
Grommes, J. et al. Contribution of neutrophils to acute lung injury. Mol. Med. 17, 293–307 (2011).
pubmed: 21046059
doi: 10.2119/molmed.2010.00138
Williams, A. E. et al. The mercurial nature of neutrophils: still an enigma in ARDS? Am. J. Physiol. Lung Cell Mol. Physiol. 306, L217–L230 (2014).
pubmed: 24318116
doi: 10.1152/ajplung.00311.2013
Zhou, X. et al. Neutrophils in acute lung injury. Front. Biosci. (Landmark Ed). 17, 2278–2283 (2012).
pubmed: 22652778
doi: 10.2741/4051
Kangelaris, K. N. et al. Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS. Am. J. Physiol. Lung Cell Mol. Physiol. 308, L1102–L1113 (2015).
pubmed: 25795726
pmcid: 4451399
doi: 10.1152/ajplung.00380.2014
Mitroulis, I. et al. Developmental endothelial locus-1 attenuates complement-dependent phagocytosis through inhibition of Mac-1-integrin. Thromb. Haemost. 111, 1004–1006 (2014).
pubmed: 24352615
doi: 10.1160/TH13-09-0794
Chavakis, T. et al. Hematopoietic progenitor cells as integrative hubs for adaptation to and fine-tuning of inflammation. Nat. Immunol. 20, 802–811 (2019).
pubmed: 31213716
pmcid: 6709414
doi: 10.1038/s41590-019-0402-5
Boll, I. T. et al. A kinetic model of granulocytopoiesis. Exp. Cell Res. 61, 147–152 (1970).
pubmed: 4914506
doi: 10.1016/0014-4827(70)90268-5
Lawrence, S. M. et al. Age-appropriate functions and dysfunctions of the neonatal neutrophil. Front. Pediatr. 5, 23 (2017).
pubmed: 28293548
pmcid: 5329040
doi: 10.3389/fped.2017.00023
Carr, R. Neutrophil production and function in newborn infants. Br. J. Haematol. 110, 18–28 (2000).
pubmed: 10930976
doi: 10.1046/j.1365-2141.2000.01992.x
Nakamura-Ishizu, A. et al. Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration. Blood. 119, 5429–5437 (2012).
pubmed: 22553313
pmcid: 3418770
doi: 10.1182/blood-2011-11-393645
Winkler, I. G. et al. Vascular niche E-selectin regulates hematopoietic stem cell dormancy, self-renewal and chemoresistance. Nat. Med. 18, 1651–1657 (2012).
pubmed: 23086476
doi: 10.1038/nm.2969
Lee, G. Y. et al. Age-related differences in the bone marrow stem cell niche generate specialized microenvironments for the distinct regulation of normal hematopoietic and leukemia stem cells. Sci Rep. 9, 1007 (2019).
pubmed: 30700727
pmcid: 6353913
doi: 10.1038/s41598-018-36999-5
Penaloza, H. F. et al. Interleukin-10 plays a key role in the modulation of neutrophils recruitment and lung inflammation during infection by Streptococcus pneumoniae. Immunology. 146, 100–112 (2015).
pubmed: 26032199
pmcid: 4552505
doi: 10.1111/imm.12486
Andrade, E. B. et al. TLR2-induced IL-10 production impairs neutrophil recruitment to infected tissues during neonatal bacterial sepsis. J. Immunol. 191, 4759–4768 (2013).
pubmed: 24078699
doi: 10.4049/jimmunol.1301752
Lally, K. P. et al. The role of anti-tumor necrosis factor-alpha and interleukin-10 in protecting murine neonates from Escherichia coli sepsis. J. Pediatr. Surg. 35, 852–855 (2000).
pubmed: 10873025
doi: 10.1053/jpsu.2000.6862
Cusumano, V. et al. Interleukin-10 protects neonatal mice from lethal group B streptococcal infection. Infect. Immun. 64, 2850–2852 (1996).
pubmed: 8698523
pmcid: 174154
doi: 10.1128/iai.64.7.2850-2852.1996
Al-Mulla, Z. S. et al. Neutropenia in the neonate. Clin. Perinatol. 22, 711–739 (1995).
pubmed: 8521690
doi: 10.1016/S0095-5108(18)30277-X
Carr, R. et al. Low soluble FcRIII receptor demonstrates reduced neutrophil reserves in preterm neonates. Arch. Dis. Child Fetal Neonatal Ed. 83, F160 (2000).
pubmed: 11012271
pmcid: 1721145
doi: 10.1136/fn.83.2.F160
Rincon, J. C. et al. Cecal slurry injection in neonatal and adult mice. Methods Mol. Biol. 2321, 27–41 (2021).
pubmed: 34048005
pmcid: 8482797
doi: 10.1007/978-1-0716-1488-4_4
Nandi, M. et al. Rethinking animal models of sepsis—working towards improved clinical translation whilst integrating the 3Rs. Clin. Sci. 134, 1715–1734 (2020).
doi: 10.1042/CS20200679
Chaudhuri, J. et al. Granulocyte colony-stimulating factor for preterms with sepsis and neutropenia: a randomized controlled trial. J. Clin. Neonatol. 1, 202–206 (2012).
pubmed: 24027727
pmcid: 3762052
doi: 10.4103/2249-4847.105993
Carr, R. et al. Granulocyte-macrophage colony stimulating factor administered as prophylaxis for reduction of sepsis in extremely preterm, small for gestational age neonates (the PROGRAMS trial): a single-blind, multicentre, randomised controlled trial. Lancet 373, 226–233 (2009).
pubmed: 19150703
doi: 10.1016/S0140-6736(09)60071-4
Starr, M. E. et al. A new cecal slurry preparation protocol with improved long-term reproducibility for animal models of sepsis. PLoS One 9, e115705 (2014).
pubmed: 25531402
pmcid: 4274114
doi: 10.1371/journal.pone.0115705
Brook, B. et al. Controlled mouse model for neonatal polymicrobial sepsis. J. Vis. Exp. 143, e58574 (2019).
Bradley, P. P. et al. Cellular and extracellular myeloperoxidase in pyogenic inflammation. Blood. 60, 618–622 (1982).
pubmed: 6286012
doi: 10.1182/blood.V60.3.618.618
Pfaffl, M. W. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29, e45 (2001).
pubmed: 11328886
pmcid: 55695
doi: 10.1093/nar/29.9.e45