Journal of Cell Biology & Immunology
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on Medical, Pharma, Engineering, Science, Technology and Business
  • Editorial   
  • J Cell Biol Immunol 2017, Vol 1(1): e103

Neutrophils are very Interesting Cells

Novak ITC* and Rodriguez FM
Institute of Cell Biology, Faculty of Medical Sciences, National University of Cordoba, Argentina
*Corresponding Author: Novak ITC, Institute of Cell Biology, Faculty of Medical Sciences, National University of Cordoba, Argentina, Tel: 00 54 351 433 4020, Email: inovak@cmefcm.uncor.edu

Received: 25-Jul-2017 / Accepted Date: 26-Jul-2017 / Published Date: 27-Jul-2017

76662

Editorial

Neutrophils have been the object of exhaustive study in recent years and they were implicated with a role in activation and regulation of innate and adaptive immunity [1].

Polymorphonuclear (PMN) neutrophils are cells that not only act as phagocytes and reactive oxygen species releasers, but also they have another function as defense mechanism called neutrophil extracellular traps (NETs), which were described by Brinkmann et al in 2004 [2]. NETs trap a wide variety of microorganisms including bacteria, viruses, fungi and parasites. NETs have not only been involved as defense mechanisms, but they have also been linked to autoimmunity, cancer immunoediting [3], tissue damage and thrombosis [4]. NETs are constituted by chromatin and granular proteins, and they can be generated in inflammatory conditions [5,6]. It has been observed, as a sterile stimulus, that the monosodium urate crystals in patients with gout trigger the formation of NETs [7].

Stunningly, neutrophil leukocytes are able to express Major Histocompatibility Complex class II (DR) antigen (HLA-DR) and the costimulatory molecules CD80 and CD86 on their surface, which enables them as potential antigen-presenting cells (APC) [8,9]. The B7-1 (CD80)/B7-2 (CD86):CD28/CTLA-4 pathway is the best characterized T-cell costimulatory pathway [10,11]. Recently we found CD80 and CD86 colocalized in NETs in autologous leukocytes cultures, after lipopolysaccharide (LPS) or ovalbumin (OVA) stimulation [12,13]. The presence of costimulatory molecules in NETs would have implications for the rupture of self-tolerance, which in future investigations could contribute to explain the immunopathogenesis of autoimmune diseases.

The presence of these molecules in the cellular microenvironment can determine the stimulation or inhibition of the immune response, considering the complexity of diverse populations of T cells, naives and effectors [14]. The neutrophil phenotype as a probable APC has been described on in vitro and in vivo activated human PMN and in murine models with the expression of HLA-DR, CD80 and CD86 molecules [8,15].

All these antecedents give rise to multiple and varied questions to be elucidated by the scientific researchers, includes us. In agree with the results of several research papers, arises the concept of "neutrophil phenotypes", but there are heterogenea descriptions in literature, because parameters, methods, specie, tissue, biomarkers, are different [16].

Argentina is one of the countries with high prevalence of Chagas' disease. Chagas disease is a parasitic disease produced by the protozoan Trypanosoma cruzi and it is transmitted to humans by a blood-sucking bug of Reduviidae family [17]. It affects about 10 million people in Latin America although due to migration, it has become a global health problema [18,19]. In the chronic stage of the disease immunological cells have been implicated in the development of chagasic heart disease [20-22]. In the phathogenesis of Chagas disease has been implicated autoimmunity due to the breakdown of self-tolerance [20,22].

Neutrophils are not directly implicated in the pathophysiology; however, we have observed that in human blood samples with positive serology for Chagas disease, neutrophils have a longer half-life in autologous cultures, as well as neutrophils with ring shaped nuclei [18].

In human neutrophils ring nucleus were observed earlier by Cabral in 1987 in chagasic patients and healthy individuals [23,24]. The occurrence of extracellular traps are most commonly found in cell cultures of total blood leukocytes from chagasic patients and greater expression of CD80 was observed in LPS-stimulated leukocyte cultures of chagasic blood samples [19]. These findings could be related to the possibility of rupture of self-tolerance in agree with the autoimmunity hypothesis of immunopathogenesis of Chagas disease.

IL-10-producing neutrophils were found in a murine model of Chagas disease, and they reduce inflammation and mortality during T. cruzi infection through IL17RA-signaling [22]. Further studies are needed to elucidate the molecular mechanisms that underlie the immunopathogenesis.

On the other hand, neutrophils are very versatile cells; they are implicated in cancer, too. About of the role of PMNs in tumor development, polarization of Tumor-Associated Neutrophil (TAN) was reported [25].

Advances in neutrophil biology knowledge have made it possible to explain some pathophysiological mechanisms that were previously unclear, both in autoimmune diseases, cancer and infectious diseases. They are very interesting cells.

76663

Acknowledgments

We thank the Blood Bank, Institute of Hematology and Hemotherapy, National University of Cordoba for donation of blood samples for our research.

76664

References

  1. Mantovani A, Cassatella MA, Costantini C, Jaillon S (2011) Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol 11: 519- 531
  2. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, et al. (2004) Neutrophil extracellular traps kill bacteria. Science 303: 1532-1535.
  3. Berger-Achituv S, Brinkmann V, Abed UA, Kühn L, Ben-Ezra J, et al. (2013) A proposed role for neutrophil extracellular traps in cancer immunoediting. Front Immunol 4: 48
  4. Barrientos L, Marin-Esteban V, De Chaisemartin L, Lievin Le-Moal V, Sandré C et al. (2013) An improved strategy to recover large fragments of functional human neutrophil extracellular traps. Front Inmunol 4: 166
  5. Brinkmann V, Zychlinsky A (2012) Neutrophil extracellular traps: Is immunity the second function of chromatin? J Cell Biol 198: 773-783
  6. Papayannopoulos V, Metzler KD, Hakkim A, Zychlinsky A (2010) NE and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol 191: 677-691
  7. Schorn C, Janko C, Krenn V, Zhao Y, Munoz LE, et al. (2012) Bonding the foe - NETting neutrophils immobilize the pro-inflammatory monosodium urate crystals. Front Immunol 3: 376
  8. Sandilands GP, McCrae J, Hill K, Perry M, Baxter D (2006) Major histocompatibility complex class II (DR) antigen and costimulatory molecules on in vitro and in vivo activated human polymorphonuclear neutrophils. Immunology 119: 562-571
  9. Geng S, Matsushima H, Okamoto T, Yao Y, Lu R, et al. (2013) Emergence, origin, and function of neutrophil-dendritic cell hybrids in experimentally induced inflammatory lesions in mice. Blood 121: 1690-1700
  10. June CH, Ledbetter JA, Linsley PS, Thompson CB (1990) Role of the CD28 receptor in T-cell activation. Immunol Today 11: 211-216
  11. Brunet JF, Denizot F, Luciani MF, Roux-Dosseto M, Suzam M, et al. (1987) A new member of the immunoglobulin superfamily--CTLA-4. Nature 328: 267-270.
  12. Rodriguez FM, Novak ITC (2016) Costimulatory molecules CD80 and CD86 colocalized in neutrophil extracelular traps (NETs). J Immunol Infect Dis 3: 1-9.
  13. Rodríguez FM, Novak ITC (2016) May NETs Contain Costimulatory Molecules. J ImmunoBiol1: 4
  14. Chen L, Flies DB (2013) Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol 13: 227-242.
  15. Culshaw S, Millington OR, Brewer JM, McInnes IB (2008) Murine neutrophils present Class II restricted antigen. Immunol Lett 118: 49-54.
  16. Rodriguez FM, Novak ITC (2017) What about the neutrophils phenotypes? Hematol Med Oncol 2.
  17. Coura JR (2015) The main sceneries of Chagas disease transmission. The vectors, blood and oral transmissions--a comprehensive review. Mem Inst Oswaldo Cruz 110: 277-282
  18. Rodriguez FM, Orquera AD, Maturano MR, Infante NS, Carabajal-Miotti C, et al. (2016) Human Neutrophils in Patients with Positive Serology for Chagas Disease. J Immunol Infect Dis 3: 101.
  19. Rodriguez FM, Vargas A, Miotti CC, Silva NG, Frattari SR, et al. (2017) Extracellular Traps and Co-Stimulatory Molecules in Leukocytes of Patients with Positive Serology for Chagas Disease. MOJ Immunol 5: 00163
  20. Cabral HR (1969) Los mecanismos patogenéticos del daño tisular en la enfermedad de Chagas. Rev Fac Cienc Med Univ Nac Córdoba 27: 287-309.
  21. Cabral HR (1971) PAS-positive substance in lymphocytes of patients with Chagas disease. Lancet 1: 1356-1357.
  22. Tosello-Boari J, Vesely MCA, Bermejo DA, Ramello MC, Montes CL, et al. (2012) IL-17RA Signaling Reduces inflammation and mortality during Trypanosoma cruzi infection by recruiting suppressive IL- 10-producing neutrophils. PLoS Pathog 8: e1002658.
  23. Cabral HRA (1987) Neutrophils with ring-shaped nuclei in human Chagas’ disease. Br J Haematol 67: 118-119.
  24. Cabral HR, Robert GB (1989) Ring-shaped nuclei in human neutrophilic leukocytes of healthy individuals: evidence of their occurrence and characteristics. Am J Hematol 30: 259-260.
  25. Fridlender Zvi G, Sun J, Kim S, Kapoor V, Cheng G, et al. (2009) Polarization of Tumor-Associated Neutrophil (TAN) Phenotype by TGF-ß: “N1” versus “N2” TAN. Cancer Cell 16: 183-194.

Citation: Novak ITC, Rodriguez FM (2017) Neutrophils are very Interesting Cells. J Cell Biol Immunol 1: e103

Copyright: ©2017 Novak ITC, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Top