Effects of Maternal Immune System Status on Neonate’s Immune System

Document Type : Original Article

Authors

1 Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz,Ahvaz, Iran

2 Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz,Ahvaz, Iran

3 Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz ,Iran. Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

4 Department of Histology, Faculty of Medicine, Dezful University of Medical Sciences, Dezful, Iran

Abstract

Background: This study evaluated the effects of the maternal immune system stimulation or suppression during the pregnancy on the development of the neonate’s immune system.
Methods: A total of 20 female rats were divided into four groups. The groups were treated using Leishmania major, Salmonella typhimurium, Tacrolimus, and sterilized normal saline. The animals were mated after 3-time treatments. The neonate’s humoral immune response, total body, thymus, liver, spleen weight, and histology were determined in this study.
Results: The spleen’s mean weight of the two-month-old samples showed a significant reduction in the Salmonella group; in addition, the Tacrolimus group had a significant reduction in liver mean weight. The Salmonella and Tacrolimus groups showed a significant reduction (P≤0.05) in the anti-sheep red blood cells antibody titer.
Conclusion: Stimulation or suppression of the immune responses during the pregnancy has significant effects on the neonate’s immune responses, spleen, liver, and thymus development.

Keywords


1. Holladay SD, Sharova LV, Punareewattana K, Hrubec TC, Gogal RM Jr, Prater MR, et al. Maternal immune stimulation in mice decreases fetal malformations caused by teratogens. Int Immunopharmacol. 2002; 2(2-3):325-32.
2. Hodgson E, Mailman RB, Chambers JE. Dictionary of toxicology. New York: Macmillan; 1998. P. 450.
3. Svensson-Arvelund J, Ernerudh J, Buse E, Cline JM, Haeger JD, Dixon D, et al. The placenta in toxicology. Part II: systemic and local immune adaptations in pregnancy. Toxicol Pathol. 2014; 42(2):327-38.
4. Hsu P, Nanan R. Foetal immune programming: hormones, cytokines, microbes and regulatory T cells. J Reprod Immunol. 2014; 104-105:2-7.
5. Morelli S, Mandal M, Goldsmith LT, Kashani BN, Ponzio NM. The maternal immune system during pregnancy and its influence on fetal development. Res Rep Biol. 2015; 6:171-89.
6. King A. Uterine leukocytes and decidualization. Hum Reprod Update. 2000; 6(1):28-36.
7. Mor G, Cardenas I. The immune system in pregnancy: a unique complexity. Am J Reprod Immunol. 2010; 63(6):425-33.
8. Marques AH, OConnor TG, Roth C, Susser E, Bjorke-Monsen AL. The influence of maternal prenatal and early childhood nutrition and maternal prenatal stress on offspring immune system development and neurodevelopmental disorders. Front Neurosci. 2013; 7:120.
9. Brown AS, Begg MD, Gravenstein S, Schaefer CA, Wyatt RJ, Bresnahan M, et al. Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry. 2004; 61(8):774-80.
10. Bilbo SD, Schwarz JM. The immune system and developmental programming of brain and behavior. Front Neuroendocrinol. 2012; 33(3):267-86.
11. Smith SE, Li J, Garbett K, Mirnics K, Patterson PH. Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci. 2007; 27(40):10695-702.
12. Ponzio NM, Servatius R, Beck K, Marzouk A, Kreider T. Cytokine levels during pregnancy influence immunological profiles and neurobehavioral patterns of the offspring. Ann N Y Acad Sci. 2007; 1107:118-28.
13. Pashine A, John B, Rath S, George A, Bal V. Th1 dominan
ce in the immune response to live Salmonella typhimurium requires bacterial invasiveness but not persistence. Int Immunol. 1999; 11(4):481-9.
14. Okwor I, Liu D, Uzonna J. Qualitative differences in the early immune response to live and killed Leishmania major: Implications for vaccination strategies against Leishmaniasis. Vaccine. 2009; 27(19):2554-62.
15. Kainz A, Harabacz I, Cowlrick IS, Gadgil S, Hagiwara D. Analysis of 100 pregnancy outcomes in women treated systemically with tacrolimus. Transpl Int. 2000; 13(Suppl 1):S299-300.
16. Reyes TM, Coe CL. Prenatal manipulations reduce the proinflammatory response to a cytokine challenge in juvenile monkeys. Brain Res. 1997; 769(1):29-35.
17. Beloosesky R, Maravi N, Weiner Z, Khatib N, Awad N, Boles J, et al. Maternal lipopolysaccharide-induced inflammation during pregnancy programs impaired offspring innate immune responses. Am J Obstet Gynecol. 2010; 203(2):185.e1-4.
18. Coe CL, Kramer M, Kirschbaum C, Netter P, Fuchs E. Prenatal stress diminishes the cytokine response of leukocytes to endotoxin stimulation in juvenile rhesus monkeys. J Clin Endocrinol Metab. 2002; 87(2):675-81.
19. Hodyl NA, Krivanek KM, Lawrence E, Clifton VL, Hodgson DM. Prenatal exposure to a pro-inflammatory stimulus causes delays in the development of the innate immune response to LPS in the offspring. J Neuroimmunol. 2007; 190(1-2):61-71.
20. Xiong F, Zhang L. Role of the hypothalamic-pituitary-adrenal axis in developmental programming of health and disease. Front Neuroendocrinol. 2012; 34(1):27-46.
21. Palmer AC. Nutritionally mediated programming of the developing immune system. Adv Nutr. 2011; 2(5):377-95.
22. Arsenescu R, Arsenescu V, de Villiers WJ. TNF-α and the development of the neonatal immune system: implications for inhibitor use in pregnancy. Am J Gastroenterol. 2011; 106(4):559-62.
23. Svensson L, Arvola M, Sallstrom MA, Holmdahl R, Mattsson R. The Th2 cytokines IL-4 and IL-10 are not crucial for the completion of allogeneic pregnancy in mice. J Reprod Immunol. 2001; 51(1):3-7.
24. Fallon PG, Jolin HE, Smith P, Emson CL, Townsend
MJ, Fallon R, et al. IL-4 induces characteristic Th2 responses even in the combined absence of IL-5, IL-9, and IL-13. Immunity. 2002; 17(1):7-17.
25. Gomez-Lopez N, StLouis D, Lehr MA, Sanchez-Rodriguez EN, Arenas-Hernandez M. Immune cells in term and preterm labor. Cell Mol Immunol. 2014; 11(6):571-81.
26. Mandal M, Marzouk AC, Donnelly R, Ponzio NM. Maternal immune stimulation during pregnancy affects adaptive immunity in offspring to promote development of TH17 cells. Brain Behav Immun. 2011; 25(5):863-71.
27. Zaretsky MV, Alexander JM, Byrd W, Bawdon RE. Transfer of inflammatory cytokines across the placenta. Obstet Gynecol. 2004; 103(3):546-50.
28. Lip SV, van der Graaf AM, Wiegman MJ, Scherjon SA, Boekschoten MV, Plosch T, et al. Experimental preeclampsia in rats affects vascular gene expression patterns. Sci Rep. 2017; 7(1):14807.
29. Nuriel-Ohayon M, Neuman H, Koren O. Microbial changes during pregnancy, birth, and infancy. Front Microbiol. 2016; 7:1031.
30. Sharova LV, Sura P, Smith BJ, Gogal RM Jr, Sharov AA, Ward DL, et al. Non-specific stimulation of the maternal immune system. II. Effects on fetal gene expression. Teratology. 2000; 62(6):420-8.
31. Elledge RM, Lee WH. Life and death by p53. Bioassays. 1995; 17(11):923-30.
32. Carpentier PA, Palmer TD. Immune influence on adult neural stem cell regulation and function. Neuron. 2009; 64(1):79-92.
33. Yan WU. Impact of prenatal stress and adulthood stress on immune system: a review. Biomed Res. 2012; 23(3):315-20.
34. Suda T, Murray R, Fischer M, Yokota T, Zlotnik A. Tumor necrosis factor a and P40 induce day15 murine fetal thymocyte proliferation in combination with IL-2. J Immunol. 1990; 144(5):1783-7.
35. Wen L, Shinton SA, Hardy RR, Hayakawa K. Association of B-1 B cells with follicular dendritic cells in spleen. J Immunol. 2005; 174(11):6918-26.
36. Randall TD, Carragher DM, Rangel-Moreno J. Development of secondary lymphoid organs. Annu Rev Immunol. 2008; 26:627-50.
37. Jacob C, Hoab T, Karimiab K, Arckab PC. Fetal origin of chronic immune diseases: role of prenatal stress challenge. J Reprod Immunol. 2010; 86:91-2.
38. Nevers W, Pupco A, Koren G, Bozzo P. Safety of tacrolimus in pregnancy. Can Fam Physician. 2014; 60(10):905-6.