Hostname: page-component-cd9895bd7-gvvz8 Total loading time: 0 Render date: 2024-12-28T18:23:23.209Z Has data issue: false hasContentIssue false
  • English
  • Français

Heat stress upregulation of Toll-like receptors 2/4 and acute inflammatory cytokines in peripheral blood mononuclear cell (PBMC) of Bama miniature pigs: an in vivo and in vitro study

Published online by Cambridge University Press:  10 June 2014

X.-H. Ju ,
H.-J. Xu ,
Y.-H. Yong ,
L.-L. An ,
P.-R. Jiao  and
M. Liao
X.-H. Ju
Affiliation:
Department of Veterinary Medicine, Guangdong Ocean University, Zhanjiang 524088, China MOA Key Laboratory for Animal Vaccine Development, Key Laboratory of Zoonoses Control and Prevention of Guangdong, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
H.-J. Xu
Affiliation:
Department of Animal Science, Guangdong Ocean University, Zhanjiang 524088, China
Y.-H. Yong
Affiliation:
Department of Veterinary Medicine, Guangdong Ocean University, Zhanjiang 524088, China
L.-L. An
Affiliation:
Department of Animal Science, Guangdong Ocean University, Zhanjiang 524088, China
P.-R. Jiao
Affiliation:
MOA Key Laboratory for Animal Vaccine Development, Key Laboratory of Zoonoses Control and Prevention of Guangdong, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
M. Liao*
Affiliation:
MOA Key Laboratory for Animal Vaccine Development, Key Laboratory of Zoonoses Control and Prevention of Guangdong, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
*
† E-mail: mliaoscau@gmail.com
Get access

Abstract

Global warming is a challenge to animal health, because of increased heat stress, with subsequent induction of immunosuppression and increased susceptibility to disease. Toll-like receptors (TLR) are pattern recognition receptors that act as sentinels of pathogen invasion and tissue damage. Ligation of TLRs results in a signaling cascade and production of inflammatory cytokines, which eradicate pathogens and maintain the health of the host. We hypothesized that the TLR signaling pathway plays a role in immunosuppression in heat-stressed pigs. We explored the changes in the expression of TLR2, TLR4 and the concentration of acute inflammatory cytokines, such as IL-2, IL-8, IL-12 and IFN-γ in Bama miniature pigs subjected to 21 consecutive days of heat stress, both in vitro and in vivo models. The results showed that heat stress induced the upregulation of cortisol in the plasma of pigs (P<0.05); TLR4 mRNA was elevated, but IL-2 was reduced in peripheral blood mononuclear cells (PBMC, P<0.05). The white blood cell count and the percentage of granulocytes (eosinophilic+basophilic) decreased significantly in heat-stressed pigs (P<0.05). In the in vitro model (PBMC heat shocked for 1 h followed by a 9 h recovery period), TLR2 and TLR4 mRNA expression also increased, as did the concentration of IL-12 in supernatants. However, IFN-γ was significantly reduced in PBMC culture supernatants (P<0.05). We concluded that a consecutive heat stress period elevated the expression of TLR2 and TLR4 in PBMC and increased the plasma levels of inflammatory cytokines. These data indicate that TLR activation and dysregulation of cytokine expression in response to prolonged heat stress may be associated with immunosuppression and increased susceptibility to antigenic challenge in Bama miniature pigs.

Keywords

Bama miniature pigheat stressinflammatory cytokineToll-like receptors
Type
Research Article
Information
animal , Volume 8 , Issue 9 , September 2014 , pp. 1462 - 1468
Copyright
© The Animal Consortium 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Becker, BA, Nienaber, JA, Christenson, RK, Manak, RC, DeShazer, JA and Hahn, GL 1985. Peripheral concentrations of cortisol as an indicator of stress in the pig. American Journal of Veterinary Research 46, 1034.Google Scholar
Chen, W, Wang, J, An, H, Zhou, J, Zhang, L and Cao, X 2005. Heat shock up-regulates TLR9 expression in human B cells through activation of ERK and NF-κB signal pathways. Immunology Letters 98, 153–159.Google Scholar
Doukas, J, Hechtman, HB and Shepro, D 1988. Endothelial-secreted arachidonic acid metabolites modulate polymorphonuclear leukocyte chemotaxis and diapedesis in vitro . Blood 71, 771–779.CrossRefGoogle ScholarPubMed
Eicher, S, Sartin, J, Schwartz, D, Lay, D Jr and Cheng, HW 2004. Toll-like receptors 2 (TLR2) and 4 (TLR4) of porcine blood leukocytes during heat-stress. In Veterinary Immunology International Symposium (Abstract), p. 240.Google Scholar
Farooq, U, Samad, HA, Shehzad, F and Qayyum, A 2010. Physiological responses of cattle to heat stress. World Applied Sciences Journal 8, 38–43.Google Scholar
Hermann, G, Amy Tovar, C, Michael Beck, F, Allen, C and Sheridan, JF 1993. Restraint stress differentially affects the pathogenesis of an experimental influenza viral infection in three inbred strains of mice. Journal of Neuroimmunology 47, 83–93.Google Scholar
Hicks, TA, McGlone, JJ, Whisnant, CS, Kattesh, HG and Norman, RL 1998. Behavioral, endocrine, immune, and performance measures for pigs exposed to acute stress. Journal of Animal Science 76, 474–483.Google Scholar
Hyun, Y, Ellis, M, Riskowski, G and Johnson, RW 1998. Growth performance of pigs subjected to multiple concurrent environmental stressors. Journal of Animal Science 76, 721–727.Google Scholar
Inohara, N, Ogura, Y, Fontalba, A, Gutierrez, O, Pons, F, Crespo, J, Fukase, K, Inamura, S, Kusumoto, S and Hashimoto, M 2003. Host recognition of bacterial muramyl dipeptide mediated through NOD2. Journal of Biological Chemistry 278, 5509–5512.CrossRefGoogle ScholarPubMed
Ju, X-H, Yong, Y-H, Xu, H-J, An, L-l and Xu, Y-M 2011a. Impacts of heat stress on baseline immune measures and a subset of T cells in Bama miniature pigs. Livestock Science 135, 289–292.Google Scholar
Ju, X-H, Yong, Y-H, Xu, H-J, An, L-l, Xu, Y-M, Jiao, P-R and Liao, M 2011b. Selection of reference genes for gene expression studies in PBMC from Bama miniature pig under heat stress. Veterinary Immunology and Immunopathology 144, 160–166.Google Scholar
Kamstrup, S, Verthelyi, D and Klinman, DM 2001. Response of porcine peripheral blood mononuclear cells to CpG-containing oligodeoxynucleotides. Veterinary Microbiology 78, 353–362.Google Scholar
Kauffmann, F, Neukirch, F, Annesi, I, Korobaeff, M, Dor, MF and Lellouch, J 1988. Relation of perceived nasal and bronchial hyperresponsiveness to FEV1, basophil counts, and methacholine response. Thorax 43, 456–461.CrossRefGoogle ScholarPubMed
Kelley, KW 1985. Immunological consequences of changing environmental stimuli. In Animal Stress (ed. GP Moberg), pp. 193–223. American Physiological Society, Bethesda, MD.Google Scholar
Lee, JA, Roussel, JD and Beatty, JF 1976. Effect of temperature-season on bovine adrenal cortical function, blood cell profile, and milk production. Journal of Dairy Science 59, 104–108.Google Scholar
Li, CL, Wang, XY, Shao, J, Zhang, JS, Feng, WG, Wang, YB and Chang, ZL 2001. Heat shock inhibits IL-12 p40 expression through NF-κB signalling pathway in murine macrophages. Cytokine 16, 153–159.Google Scholar
Lv, Q, Zhang, S and Zhao, R 2011. Transportation stress alters the expression of immunoregulatory cytokines in the porcine thymus. The Veterinary Journal 187, 229–233.CrossRefGoogle ScholarPubMed
Marchini, CFP, Nascimento, M, Silva, PL and Guimares, EC 2011. Hematologic parameters in broilers subjected to cyclic heat stress. Retrieved October 20, 2011, from http://en.engormix.com/MA-poultry-industry/management/articles/hematologic-parameters-broilers-subjected-t1803/124-p0.htm.Google Scholar
Marsh, BJ, Williams-Karnesky, RL and Stenzel-Poore, MP 2009. Toll-like receptor signaling in endogenous neuroprotection and stroke. Neuroscience 158, 1007–1020.Google Scholar
Mostefaoui, Y, Bart, C, Frenette, M and Rouabhia, M 2004. Candida albicans and Streptococcus salivarius modulate IL-6, IL-8 and TNF-alpha expression and secretion by engineered human oral mucosa cells. Cellular Microbiology 6, 1085–1096.CrossRefGoogle ScholarPubMed
O’Connor, TM, O’Halloran, DJ and Shanahan, F 2000. The stress response and the hypothalamic-pituitary-adrenal axis: from molecule to melancholia. Qjm 93, 323–333.Google Scholar
O’Neill, LAJ 2006. How Toll-like receptors signal: what we know and what we don’t know. Current Opinion in Immunology 18, 3–9.Google Scholar
Panes, J, Perry, M and Granger, DN 2009. Leukocyte-endothelial cell adhesion: avenues for therapeutic intervention. British Journal of Pharmacology 126, 537–550.CrossRefGoogle Scholar
Parrott, RF and Misson, BH 1989. Changes in pig salivary cortisol in response to transport simulation, food and water deprivation, and mixing. British Veterinary Journal 145, 501–505.CrossRefGoogle ScholarPubMed
Reddy, NR and Wilkie, BN 2000. Quantitation of porcine cytokine and beta 2-microglobulin mRNA expression by reverse transcription polymerase chain reaction. Journal of Immunological Methods 233, 83–93.Google Scholar
Ross, JS, Bacon, KB and Camp, RDR 1990. Potent and selective inhibition of in vitro lymphocyte migration by cyclosporine and dexamethasone. Immunopharmacology and Immunotoxicology 12, 439–455.Google Scholar
Schwartz, RH 1990. A cell culture model for T lymphocyte clonal anergy. Science 248, 1349.Google Scholar
St-Pierre, NR, Cobanov, B and Schnitkey, G 2003. Economic losses from heat stress by US livestock industries. Journal of Dairy Science 86, E52–E77.Google Scholar
Sun, D, Chen, D, Du, B and Pan, J 2005. Heat shock response inhibits NF-κB activation and cytokine production in murine Kupffer cells. Journal of Surgical Research 129, 114–121.Google Scholar
Sutherland, MA, Niekamp, SR, Rodriguez-Zas, SL and Salak-Johnson, JL 2006. Impacts of chronic stress and social status on various physiological and performance measures in pigs of different breeds. Journal of Animal Science 84, 588–596.Google Scholar
Wang, Y, Seidl, T, Whittall, T, Babaahmady, K and Lehner, T 2010. Stress-activated dendritic cells interact with CD4+ T cells to elicit homeostatic memory. European Journal of Immunology 40, 1628–1638.Google Scholar
Williams, TJ 1990. Effect of glucocorticoids on microvascular permeability. American Review Respiratory Disease S39–S43.Google ScholarPubMed
Zhang, G and Ghosh, S 2001. Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity. Journal of Clinical Investigation 107, 13–20.Google Scholar
Zhang, Y, Miao, J, Hanley, G, Stuart, C, Sun, X, Chen, T and Yin, D 2008. Chronic restraint stress promotes immune suppression through Toll-like receptor 4-mediated phosphoinositide 3-kinase signaling. Journal of Neuroimmunology 204, 13–19.CrossRefGoogle ScholarPubMed
Zhou, J, An, H, Xu, H, Liu, S and Cao, X 2005. Heat shock up-regulates expression of Toll-like receptor-2 and Toll-like receptor-4 in human monocytes via p38 kinase signal pathway. Immunology 114, 522–530.CrossRefGoogle ScholarPubMed