THE FUNCTIONAL ACTIVITY OF INNATE IMMUNITY CELLS IN BACTERIAL INFECTION ON BACKGROUND OF THERMAL STRESS

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Abstract

Maintenance of thermo homeostasis under the coordinating influence of the hypothalamus is ensured by integrative interaction of various systems organisme, including the immune system. Temperature stress in infectious diseases activates the reaction of heat shock, the biochemical consequence of which is the initiation of the organism’s defense against the pathogen. Cells of innate immunity (neutrophils and macrophages) are the first line of protection against pathogenic agents and play a primary role in the development of bacterial infections. Of particular interest is the study of the duration of the effect of hyperthermia to achieve a balance between the bioenergetic costs of these cells, as well as the study of the course of the pathological process in an organism previously exposed to hige temperature. The functional status of neutrophils and macrophages, including phagocytosis, the activity of enzymes of the oxygen-dependent system: lactate dehydrogenase, cytochrome oxidase, myeloperoxidase, cellular stimulation (intracellular AMPase content) and the content of nitrogen oxide metabolites have been studied in the model of animals exposed to low and high temperatures. It has been established that under hyperthermia conditions, the change in the functional activity of cells by enzyme level is more pronounced than when exposed to animals with low temperature, especially 4 h exposure. In animals pre-exposed to heat stress, manifestations of pseudotuberculosis infection were more severe with an increase in mortality rates by 2.6 times, compared to animals infected by bacteria. These animals had a high stimulation of effector cells of inflammation in the initial periods (at 7 days) their metabolism was enhanced, which was expressed of the activity of enzymes of the oxygen-dependent system, as well as in high nitroxide-producing activity. In target organs (lung, liver, spleen) of experienced animals the severe disturbance of blood circulation in combination with significant destructive changes typical for generalized infection were showed. At dead animals on the background of marked hemorrhagic component pathological process and weak cell inflammatory response observed depletion of the immune system (delimphatization), indicating a decrease in defense reactions and the development of immunodeficiency. Thus, under conditions of heat stress (+30°С), the intensity of the reaction of innate immunity cells in terms of enzyme’s functional activity was higher than when exposed to animals of low temperature (+4°C). Under these temperature conditions, a high level of cell priming was determined, which reduced their killing potential. These data indicate the adequacy of the model used to reproduce induced secondary immunodeficiency in a congenital defense system. Moreover, in the pathogenesis of pseudotuberculosis infection against the background of prolonged action high temperature, the effects of phagocytes oxidative stress in the structural changes of immunocompetent organs were detected.

About the authors

N. G. Plekhova

Central Research Laboratory, Pacific State Medical University

Author for correspondence.
Email: pl_nat@hotmail.com

Natalia G. Plekhova

690002, Vladivostok, Ostryakova pr., 4, Phone: +7 (423) 242-97-78 (office)

Russian Federation

L. M. Somova

Research Somov Institute of Epidemiology and Microbiology

Email: fake@neicon.ru

PhD, MD (Medicine), Professor, Chief Researcher, Laboratory of Cellular Biology and Histopathology.

Vladivostok

Russian Federation

E. I. Drobot

Research Somov Institute of Epidemiology and Microbiology

Email: fake@neicon.ru

PhD (Biology), Researcher, Laboratory of Cellular Biology and Histopathology.

Vladivostok 

Russian Federation

A. V. Lagureva

Central Research Laboratory, Pacific State Medical University

Email: fake@neicon.ru

Junior Researcher, Central Research Laboratory.

Vladivostok Russian Federation

I. N. Lyapun

Research Somov Institute of Epidemiology and Microbiology

Email: fake@neicon.ru

PhD (Biology), Head of the Laboratory of Cellular Biology and Histopathology.

Vladivostok Russian Federation

N. M. Kondrashova

Central Research Laboratory, Pacific State Medical University

Email: fake@neicon.ru

PhD (Medicine), Associate Professor, Institute of Therapy and Instrumental Diagnostics.

Vladivostok Russian Federation

S. D. Ogneva

Central Research Laboratory, Pacific State Medical University

Email: fake@neicon.ru

PhD Student, Central Research Laboratory.

Vladivostok Russian Federation

References

  1. Баллюзек Ф.В., Баллюзек М.Ф., Виленский В.И., Горелов С.И., Жигалов С.А., Иванов А.А., Кузьмин С.Н., Определяков Г.А. Управляемая гипертермия. СПб.: Невский диалект, 2001. 110 с.
  2. Мичурина С.В., Васендин Д.В., Ищенко И.Ю., Жданов А.П. Структурные изменения в тимусе крыс после воздействия экспериментальной гипертермии // Бюллетень Волгоградского научного центра РАМН. 2010. № 1 (25). С. 30–33.
  3. Arons M.M., Wheeler A.P., Bernard G.R., Christman B.W., Russell J.A., Schein R., Summer W.R., Steinberg K.P., Fulkerson W., Wright P., Dupont W.D., Swindell B.B. Effects of ibuprofen on the physiology and survival of hypothermic sepsis. Ibuprofen in Sepsis Study Group. Crit. Care Med., 1999, vol. 27, iss. 4, pp. 699–707. doi: 10.1097/00003246-199904000-00020
  4. Casadevall A. Thermal restriction as an antimicrobial function of fever. PLoS Pathog., 2016, vol. 12, no. 5:e1005577. doi: 10.1371/journal.ppat.1005577
  5. Evans S.S., Repasky E.A., Fisher D.T. Fever and the thermal regulation of immunity: the immune system feels the heat. Nat. Rev. Immunol., 2015, vol. 15, no. 6, pp. 335–349. doi: 10.1038/nri3843
  6. Frey B., Weiss E.M., Rubner Y., Wunderlich R., Ott O.J., Sauer R., Fietkau R., Gaipl U.S. Old and new facts about hyperthermia-induced modulations of the immune system. Int. J. Hyperthermia, 2012, vol. 28, iss. 6, pp. 528–542. doi: 10.3109/02656736.2012.677933
  7. Fisher D.T., Chen Q., Skitzki J.J., Muhitch J.B., Zhou L., Appenheimer M.M., Vardam T.D., Weis E.L., Passanese J., Wang W.C., Gollnick S.O., Dewhirst M.W., Rose-John S., Repasky E.A., Baumann H., Evans S.S. IL-6 trans-signaling licenses mouse and human tumor microvascular gateways for trafficking of cytotoxic T cells. J. Clin. Invest., 2011, vol. 121, no. 10, pp. 3846–3859. doi: 10.1172/JCI44952
  8. Grunwald M.S., Pires A.S., Zanotto-Filho A., Gasparotto J., Gelain D.P., Demartini D.R., Scholer C.M., de Bittencourt P.I.Jr., Moreira J.C. The oxidation of HSP70 is associated with functional impairment and lack of stimulatory capacity. Cell Stress Chaperones, 2014, vol. 19, iss. 6, pp. 913–925. doi: 10.1007/s12192-014-0516-5
  9. Hasday J.D., Thompson C., Singh I.S. Fever, immunity, and molecular adaptations. Compr. Physiol., 2014, vol. 4, pp. 109–148. doi: 10.1002/cphy.c130019
  10. Hevia A., Delgado S., Sanchez B., Margolles A. Molecular players involved in the interaction between beneficial bacteria and the immune system. Front. Microbiol., 2015, vol. 6:1285. doi: 10.3389/fmicb.2015.01285
  11. Hume D.A. The many alternative faces of macrophage activation. Front. Immunol., 2015, vol. 6:370. doi: 10.3389/fimmu.2015.00370
  12. Jaillon S., Galdiero M.R., Del Prete D., Cassatella M.A., Garlanda C., Mantovani A. Neutrophils in innate and adaptive immunity. Semin. Immunopathol., 2013, vol. 35, iss. 4, pp. 377–394.
  13. Jin Y., Hu Y., Han D., Wang M. J. Chronic heat stress weakened the innate immunity and increased the virulence of highly pathogenic avian influenza virus H5N1 in mice. J. Biomed. Biotechnol., 2011, 10 p. doi: 10.1155/2011/367846
  14. Martinez F.O., Helming L., Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Annu. Rev. Immunol., 2009, vol. 27, pp. 451–483. doi: 10.1146/annurev.immunol.021908.132532
  15. Mikucki M.E., Fisher D.T., Ku A.W., Appenheimer M.M., Muhitch J.B, Evans S.S. Preconditioning thermal therapy: flipping the switch on IL-6 for anti-tumour immunity. Int. J. Hyperthermia, 2013, vol. 29, no. 5, pp. 464–473. doi: 10.3109/02656736.2013.807440
  16. Radek K.A. Antimicrobial anxiety: the impact of stress on antimicrobial immunity. J. Leukoc. Biol., 2010, vol. 88, no. 2, pp. 263–277. doi: 10.1189/jlb.1109740
  17. Repasky E.A., Eng J., Hylander B.L. Radek K.A. Stress, metabolism and cancer: integrated pathways contributing to immune suppression. Cancer J., 2015, vol. 21, no. 2, pp. 97–103. doi: 10.1097/ppo.0000000000000107
  18. Schmidt S., Moser M., Sperandio M. The molecular basis of leukocyte recruitment and its deficiencies. Mol. Immunol., 2013, vol. 55, no. 1, pp. 49–58. doi: 10.1016/j.molimm.2012.11.006
  19. Singh I.S., Hasday J.D. Fever, hyperthermia and the heat shock response. Int. J. Hyperthermia, 2013, vol. 29, no. 5, pp. 423–435. doi: 10.3109/02656736.2013.808766
  20. Small P.M., Tauber M.G., Hackbarth C.J., Sande M.A. Influence of body temperature on bacterial growth rates in experimental pneumococcal meningitis in rabbits. Infect. Immun., 1986, vol. 52, no. 2, pp. 484–487.
  21. Takeuchi O., Akira S. Pattern recognition receptors and inflammation. Cell, 2010, vol. 140, no. 6, pp. 805–820. doi: 10.1016/j.cell.2010.01.022
  22. Vujaskovic Z., Poulson J.M., Gaskin A.A., Thrall D.E., Page R.L., Charles H.C., MacFall J.R., Brizel D.M., Meyer R.E., Prescott D.M., Samulski T.V., Dewhirst M.W. Temperature-dependent changes in physiologic parameters of spontaneous canine soft tissue sarcomas after combined radiotherapy and hyperthermia treatment. Int. J. Radiat. Oncol. Biol. Phys., 2000, vol. 46, iss. 1, pp. 179–185. doi: 10.1016/S0360-3016(99)00362-4

Copyright (c) 2018 Plekhova N.G., Somova L.M., Drobot E.I., Lagureva A.V., Lyapun I.N., Kondrashova N.M., Ogneva S.D.

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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