Neonatal neutrophils exhibit reduced NLRP3 inflammasome activation

被引:1
作者
Wackerbarth, Lou Martha [1 ]
Seifert, Sonja Birke [1 ]
Napoli, Matteo [1 ]
Rohwedder, Ina [1 ]
Vogl, Thomas [2 ]
Scheiermann, Christoph [1 ]
Kolben, Thomas [3 ]
Nussbaum, Claudia [4 ]
Pruenster, Monika [1 ]
Immler, Roland [1 ]
Sperandio, Markus [1 ]
机构
[1] Ludwig Maximilians Univ Munchen, Inst Cardiovasc Physiol & Pathophysiol, Walter Brendel Ctr, Biomed Ctr BMC, D-82152 Planegg Martinsried, Germany
[2] Univ Munster, Inst Immunol, D-48149 Munster, Germany
[3] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Obstet & Gynecol, D-81377 Munich, Germany
[4] Ludwig Maximilians Univ Munchen, Dr von Hauner Childrens Hosp, Div Neonatol, D-81377 Munich, Germany
关键词
E-selectin; inflammation; neonatal neutrophils; NLRP3; inflammasome;
D O I
10.1093/jleuko/qiae206
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Newborns are at high risk to develop sepsis. This is linked to innate immune responses at birth which are not completely adapted to postnatal life. Neutrophils are key players of innate immunity and exhibit a marked ontogenetic regulation of their functionality. Here, we studied the NLRP3 inflammasome in neonatal neutrophils and found lower baseline expression of NLRP3, pro-caspase-1, and the K+-channel KV1.3 compared with adult neutrophils. Following stimulation with lipopolysaccharide/nigericin, apoptosis-related speck-like protein containing a caspase recruitment domain oligomerization, caspase-1 activation, and interleukin-1 beta (IL-1 beta) release were significantly reduced in neonatal compared with adult neutrophils. Similarly, stimulation of neonatal neutrophils with E-selectin led to reduced NLRP3 inflammasome activation accompanied by diminished release of the alarmin S100A8/A9. Taken together, our results strongly indicate diminished NLRP3 inflammasome activation in neonatal neutrophils leading to a significant reduction of released IL-1 beta and S100A8/A9. These findings identify reduced neutrophil NLRP3 inflammasome activation as a critical component contributing to the inherent susceptibility to infections in neonates. Cord blood neutrophils exhibit reduced NLRP3 inflammasome activation and gasdermin D pore formation upon lipopolysaccharide/nigericin or rapid E-selectin-triggered activation leading to restricted release of interleukin-1 beta and the alarmin S100A8/A9.
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页数:6
相关论文
共 14 条
[1]  
Al-Hertani W, 2007, CLIN INVEST MED, V30, pE44
[2]  
ANDERSON DC, 1991, J IMMUNOL, V146, P3372
[3]   Global incidence and mortality of neonatal sepsis: a systematic review and meta-analysis [J].
Fleischmann, Carolin ;
Reichert, Felix ;
Cassini, Alessandro ;
Horner, Rosa ;
Harder, Thomas ;
Markwart, Robby ;
Troendle, Marc ;
Savova, Yoanna ;
Kissoon, Niranjan ;
Schlattmann, Peter ;
Reinhart, Konrad ;
Allegranzi, Benedetta ;
Eckmanns, Tim .
ARCHIVES OF DISEASE IN CHILDHOOD, 2021, 106 (08) :745-752
[4]   Perinatal development of innate immune topology [J].
Henneke, Philipp ;
Kierdorf, Katrin ;
Hall, Lindsey J. ;
Sperandio, Markus ;
Hornef, Mathias .
ELIFE, 2021, 10
[5]   Differential Immune Activation in Fetal Macrophage Populations [J].
Lakhdari, Omar ;
AsamiYamamura ;
Hernandez, Gilberto E. ;
Anderson, Kathryn K. ;
Lund, Sean J. ;
Oppong-Nonterah, Gertrude O. ;
Hoffman, Hal M. ;
Prince, Lawrence S. .
SCIENTIFIC REPORTS, 2019, 9 (1)
[6]   Inflammasome activation and assembly at a glance [J].
Malik, Ankit ;
Kanneganti, Thirumala-Devi .
JOURNAL OF CELL SCIENCE, 2017, 130 (23) :3955-3963
[7]   Neutrophil and endothelial adhesive function during human fetal ontogeny [J].
Nussbaum, Claudia ;
Gloning, Anna ;
Pruenster, Monika ;
Frommhold, David ;
Bierschenk, Susanne ;
Genzel-Boroviczeny, Orsolya ;
von Andrian, Ulrich H. ;
Quackenbush, Elizabeth ;
Sperandio, Markus .
JOURNAL OF LEUKOCYTE BIOLOGY, 2013, 93 (02) :175-184
[8]   E-selectin-mediated rapid NLRP3 inflammasome activation regulates S100A8/S100A9 release from neutrophils via transient gasdermin D pore formation [J].
Pruenster, Monika ;
Immler, Roland ;
Roth, Jonas ;
Kuchler, Tim ;
Bromberger, Thomas ;
Napoli, Matteo ;
Nussbaumer, Katrin ;
Rohwedder, Ina ;
Wackerbarth, Lou Martha ;
Piantoni, Chiara ;
Hennis, Konstantin ;
Fink, Diana ;
Kallabis, Sebastian ;
Schroll, Tobias ;
Masgrau-Alsina, Sergi ;
Budke, Agnes ;
Liu, Wang ;
Vestweber, Dietmar ;
Wahl-Schott, Christian ;
Roth, Johannes ;
Meissner, Felix ;
Moser, Markus ;
Vogl, Thomas ;
Hornung, Veit ;
Broz, Petr ;
Sperandio, Markus .
NATURE IMMUNOLOGY, 2023, 24 (12) :2021-2031
[9]   A20 and the noncanonical NF-KB pathway are key regulators of neutrophil recruitment during fetal ontogeny [J].
Rohwedder, Ina ;
Wackerbarth, Lou Martha ;
Heinig, Kristina ;
Ballweg, Annamaria ;
Altstaetter, Johannes ;
Ripphahn, Myriam ;
Nussbaum, Claudia ;
Salvermoser, Melanie ;
Bierschenk, Susanne ;
Straub, Tobias ;
Gunzer, Matthias ;
Schmidt-Supprian, Marc ;
Kolben, Thomas ;
Schulz, Christian ;
Ma, Averil ;
Walzog, Barbara ;
Heinig, Matthias ;
Sperandio, Markus .
JCI INSIGHT, 2023, 8 (04)
[10]   ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation [J].
Ruhl, Sebastian ;
Shkarina, Kateryna ;
Demarco, Benjamin ;
Heilig, Rosalie ;
Santos, Jose Carlos ;
Broz, Petr .
SCIENCE, 2018, 362 (6417) :956-+