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Frontiers in immunology
2019;10 2374.

Short-Term Fever-Range Hyperthermia Accelerates NETosis and Reduces Pro-inflammatory Cytokine Secretion by Human Neutrophils.

Irene A Keitelman, Florencia Sabbione, Carolina M Shiromizu, Constanza Giai, Federico Fuentes, David Rosso, Camila Ledo, Maximiliano Miglio Rodriguez, Mauricio Guzman, Jorge R Geffner, Jeremías Galletti, Carolina Jancic, Marisa I Gómez, Analía S Trevani
Author Information
  1. Irene A Keitelman: Laboratorio de Inmunidad Innata, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
  2. Florencia Sabbione: Laboratorio de Inmunidad Innata, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
  3. Carolina M Shiromizu: Laboratorio de Inmunidad Innata, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
  4. Constanza Giai: Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM) UBA-CONICET, Buenos Aires, Argentina.
  5. Federico Fuentes: Laboratorio de Microscopía, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
  6. David Rosso: Laboratorio de Inmunidad Innata, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
  7. Camila Ledo: Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM) UBA-CONICET, Buenos Aires, Argentina.
  8. Maximiliano Miglio Rodriguez: Laboratorio de Inmunidad Innata, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
  9. Mauricio Guzman: Laboratorio de Inmunidad Innata, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
  10. Jorge R Geffner: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
  11. Jeremías Galletti: Laboratorio de Inmunidad Innata, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
  12. Carolina Jancic: Laboratorio de Inmunidad Innata, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
  13. Marisa I Gómez: Departamento de Investigaciones Biomédicas y Biotecnológicas, Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico (CEBBAD), Universidad Maimónides, Buenos Aires, Argentina.
  14. Analía S Trevani: Laboratorio de Inmunidad Innata, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
PMID: 31681277 DOI: 10.3389/fimmu.2019.02374

Abstract

Fever is a hallmark of infections and inflammatory diseases, represented by an increase of 1-4°C in core body temperature. Fever-range hyperthermia (FRH) has been shown to increase neutrophil recruitment to local sites of infection. Here, we evaluated the impact of a short period (1 h) of FRH (STFRH) on pro-inflammatory and bactericidal human neutrophil functions. STFRH did not affect neutrophil spontaneous apoptosis but reverted the lipopolysaccharide (LPS)-induced anti-apoptotic effect compared with that under normothermic conditions. Furthermore, STFRH accelerated phorbol myristate acetate (PMA)-induced NETosis evaluated either by the nuclear DNA decondensation at 2 h post-stimulation or by the increase in extracellular DNA that colocalized with myeloperoxidase (MPO) at 4 h post-stimulation. Increased NETosis upon STFRH was associated with an increase in reactive oxygen species (ROS) production but not in autophagy levels. STFRH also increased NETosis in response to challenge but moderately reduced its phagocytosis. However, these STFRH-induced effects did not influence the ability of neutrophils to kill bacteria after 4 h of co-culture. STFRH also significantly reduced neutrophil capacity to release the pro-inflammatory cytokines chemokine (C-X-C motif) ligand 8/interleukin 8 (CXCL8/IL-8) and IL-1β in response to LPS and challenge. Altogether, these results indicate that a short and mild hyperthermal period is enough to modulate neutrophil responses to bacterial encounter. They also suggest that fever spikes during bacterial infections might lead neutrophils to trigger an emergency response promoting neutrophil extracellular trap (NET) formation to ensnare bacteria in order to wall off the infection and to reduce their release of pro-inflammatory cytokines in order to limit the inflammatory response.

Keywords

NETosis NETs cytokines hyperthermia neutrophils

References

  1. J Am Soc Nephrol. 2006 May;17(5):1345-53 [PMID: 16597688]
  2. Am J Pathol. 2011 Jul;179(1):199-210 [PMID: 21703402]
  3. Infect Immun. 2000 Mar;68(3):1265-70 [PMID: 10678936]
  4. Infect Immun. 1977 Jun;16(3):947-54 [PMID: 19356]
  5. Sci Immunol. 2018 Aug 24;3(26): [PMID: 30143555]
  6. Blood. 2012 Feb 2;119(5):1214-6 [PMID: 22210873]
  7. J Infect Dis. 2003 Jun 15;187 Suppl 2:S364-9 [PMID: 12792853]
  8. Am J Respir Cell Mol Biol. 2012 Jun;46(6):807-14 [PMID: 22281986]
  9. Nat Rev Immunol. 2013 Mar;13(3):159-75 [PMID: 23435331]
  10. PLoS One. 2012;7(2):e32366 [PMID: 22389696]
  11. Cell Res. 2011 Feb;21(2):290-304 [PMID: 21060338]
  12. Am J Pathol. 2003 Jun;162(6):2005-17 [PMID: 12759256]
  13. J Immunol. 2005 Mar 15;174(6):3676-85 [PMID: 15749906]
  14. J Biomed Biotechnol. 2011;2011:284759 [PMID: 21541219]
  15. Nat Rev Immunol. 2019 Apr;19(4):255-265 [PMID: 30816340]
  16. J Immunol. 2008 Aug 15;181(4):2636-43 [PMID: 18684954]
  17. Science. 2004 Mar 5;303(5663):1532-5 [PMID: 15001782]
  18. J Innate Immun. 2017;9(4):387-402 [PMID: 28467984]
  19. Infect Immun. 1977 Dec;18(3):673-9 [PMID: 412788]
  20. J Innate Immun. 2018;10(5-6):365-372 [PMID: 29874678]
  21. Eur J Clin Invest. 2018 Nov;48 Suppl 2:e12952 [PMID: 29772063]
  22. PLoS Pathog. 2019 Jun 20;15(6):e1007812 [PMID: 31220187]
  23. J Immunol. 2009 Aug 15;183(4):2632-41 [PMID: 19620311]
  24. Cell Death Dis. 2016 Oct 27;7(10):e2437 [PMID: 27787523]
  25. Blood. 2012 Jun 28;119(26):6335-43 [PMID: 22596262]
  26. Nat Med. 2014 May;20(5):511-7 [PMID: 24784231]
  27. J Pharmacol Exp Ther. 2013 Jun;345(3):430-7 [PMID: 23536315]
  28. J Immunol. 2002 Nov 15;169(10):5396-400 [PMID: 12421912]
  29. Annu Rev Immunol. 2012;30:459-89 [PMID: 22224774]
  30. Nat Rev Immunol. 2015 Jun;15(6):335-49 [PMID: 25976513]
  31. J Cell Biol. 2007 Jan 15;176(2):231-41 [PMID: 17210947]
  32. Front Immunol. 2018 Feb 19;9:269 [PMID: 29515581]
  33. Trans Am Clin Climatol Assoc. 2011;122:34-47 [PMID: 21686207]
  34. Cell Death Differ. 2019 Mar;26(3):395-408 [PMID: 30622307]
  35. Sci Immunol. 2018 Aug 24;3(26): [PMID: 30143554]

MeSH Term

Extracellular Traps
Female
Fever
Humans
Interleukin-1beta
Interleukin-8
Male
Neutrophils
Pseudomonas Infections
Pseudomonas aeruginosa

Chemicals

CXCL8 protein, human
IL1B protein, human
Interleukin-1beta
Interleukin-8
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 2

Word Cloud

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