MODULATION OF SYSTEMIC INNATE AND ADAPTIVE IMMUNE PARAMETERS IN WEANED PIGS BY SINGLE ORAL APPLICATION OF IMMUNOBIOTICS

Hrvoje Valpotić, Renata Barić-Rafaj, Ivona Žura Žaja, Silvijo Vince, Marko Samardžija, Romana Turk, Dražen Đuričić, Tomislav Dobranić, Przemyslaw Sobiech, Luka Cvetnić, Ivica Valpotić

Abstract


The aims of this study were to evaluate the effects of peroral treatment of 4-week old pigs at weaning (Day 0) with a single dose of levamisole (LEVA) or polyoxyethyle-polyoxypropylene (POE-POP), well known immunobiotics (IBC) and promising alternatives to dietary antibiotic growth promoters (AGP), on systemic innate and adaptive immunity by determining phagocytosis (PHC) and microbicidity (MBC) efficiency of their monocytes (MO) and granulocytes (GR), changes of serum C-reactive protein (CRP) and haptoglobin (HpG) profiles and kinetics of CD4+ CD8+ T cells expression during 5 weeks following the treatments. Levels of CRP were decreased by either POE-POP or LEVA (P<0.05) at Day 7 and 21, respectively. LEVA-treated pigs had increased levels of HpG (P<0.05) at Day 14 and 21, whereas POE-POP-treated pigs had decreased and increased levels (P<0.05) at Day 7 and 21, respectively. Both IBC stimulated in vitro PHC of GR (from Day 7 to 35) and MBC of MO (at Day 35) from treated pigs (P<0.05). MO from POE-POP-treated pigs exhibited increased PHC (P<0.05) at Day 35, whereas GR from LEVA- or POE-POP-treated pigs showed increased MBC (P<0.05) at Day 7 and 35, respectively. The pigs treated by LEVA or POE-POP had higher proportions of CD4+ CD8+ T cells (P<0.05) from Day 14 to 35 or Day 28 to 35, respectively. Tested IBC showed capability of stimulating particularly cellular components of nonspecific and specific immunity during early postweaning period before pigs reach adult immunocompetence values, and thus could be considered as potent immunostimulators in swine production.

Key words: synthetic immunobiotics; innate/adaptive immunity; weaned pig


VPLIV NA SISTEMSKO PRIROJENO IN PRIDOBLJENO IMUNOST PRI ODSTAVLJENIH PUJSKIH PO ENKRATNEM DODATKU IMUNOBIOTIKOV PREKO PREBAVNEGA TRAKTA

Namen raziskave je bil ugotoviti vpliv lavamisola (LEVA) in polyoxyethylen-polyoxypropylena (POE-POP), znanih imunobiotikov, ki bi jih lahko uporabljali v praÅ¡iÄereji za boljÅ¡i prirast namesto antibiotikov, na sistemsko prirojeno in pridobljeno imunost pri odstavljenih, 4 tedne starih pujskih. Vsem živalim smo LEVA in POE-POP dajali preko ust (peroralno) in tedensko v odobju petih tednov dodajanja imunobiotikov ugotavljali stopnjo fagocitoze in protimikrobno aktivnost monocitov in granulocitov, raven serumskega C-reaktivnega proteina (CRP), profil haptoglobina (HpG) ter raven prisotnosti limfocitov T, ki izražajo gena CD4 in CD8 v krvi. Rezultati so pokazali, da je bila raven serumskega CRP znižana pri pujskih, ki so prejemali tako LEVA kot POE-POP 7. in 21. dan raziskave (p < 0,05). Pujski, ki so prejemali LEVA, so imeli zviÅ¡an HpG 14. in 21. dan raziskave (p < 0,05), medtem ko so imeli pujski, ki so prejemali POE-POP, 7. dan raziskave HpG znižan, 21. dan pa zviÅ¡an (p < 0,05). Oba imunobiotika sta v pogojih in vitro dvignila stopnjo fagocitoze pri granulocitih in protimikrobno aktivnost monocitov na 35. dan raziskave (p < 0,05). Pujski, ki so prejemali en ali drugi imunobiotik, so imeli 35. dan raziskave viÅ¡je vrednosti limfocitov T, ki so izražali CD4 in CD8, od vrednosti na 14. ali 28. dan raziskave (p < 0,05). Rezultati raziskave torej kažejo, da sta oba imunobiotika pozitivno vplivala na izbrane kazalce delovanja imunskega sistema in sta potencialno zanimiva za uporabo v praÅ¡iÄereji za spodbujanje delovanja imunskega sistema in s tem boljÅ¡i prirast praÅ¡iÄev.

KljuÄne besede: odstavljeni pujski; umetni imunobiotiki; prirojena imunost; pridobljena imunost;

Full Text:

PDF

References


(1) Sinkora J, Rehakova Z, Sinkora M, Cukrowska B, Tlaskalova-Hogenova H. Early development of immune system in pigs. Vet Immunol Immunopathol 2002; 87: 301–6.

(2) Lalles JP, Bosi P, Smidt H, Stokes CR. Weaning: a challenge to gut physiologists. Livest Sci 2007; 108: 82–93.

(3) Pomorska-Mól M, Markowska-Daniel I. Age-dependent changes in relative and absolute size of lymphocyte subsets in the blood of pigs from birth to slaughter. Bull Vet Inst Pulawy 2011; 55: 305–10.

(4) Stein HH. Experience of feeding pigs without antibiotics: a European perspective. Anim Biotechnol 2002; 13: 85–95.

(5) Gallois M, Oswald IP. Immunomodulators as efficient alternatives to in-feed antimicrobials in pig production. Arch Zootech 2008; 11: 15–32.

(6) Kogan G, Kocher A. Role of yeast cell wall polysaccharides in pig nutrition and health protection. Livest Sci 2007; 109: 161–5.

(7) Gallois M, RothkÅtter HJ, Bailey M, Stokes CR, Oswald IP. Natural alternatives to in-feed antibiotics in pig production: can immunomodulators play a role? Animal 2009; 3: 1644–61.

(8) Lalles JP, Bosi P, Janczyk P, et al. Impact of bioactive substances on the gastrointestinal tract and performance of weaned piglets: a review. Animal 2009; 3: 1625–43.

(9) Vondruskova H, Slamova R, Trckova M, Zraly Z, Pavlik I. Alternatives to antibiotic growth promoters in prevention of diarrhoea in weaned pigs: a review. Vet Med 2010; 55: 199–24.

(10) Pomorska-Mól M, Kwit K. Adjuvant properties of herbs. Med Wet 2011; 67: 449–52.

(11) Halas V, Nochta I. Mannan oligosaccharides in nursery pig nutrition and their potential mode of action. Animals 2012; 6: 261–74.

(12) Pomorska-Mól M, Kwit K, Czyżewska E, Markowska-Daniel I. Effects of dietary phytogenic product on the performance and immune response of pigs. Bull Vet Inst Pulawy 2013; 57: 381–6.

(13) Subramaniam MD, Kim IH. Clays as dietary supplements for swine: a review. J Anim Sci Biotechnol 2015; 6(1): e38 (11 pp.) https://www. ncbi.nlm.nih.gov/pmc/articles/PMC4546348/

(14) Zhang L, Xingshan T, Fengzhen Z. In vivo immunostimulatory effects of CpG ODN in newborn piglets. Mol Immunol 2007; 44: 1238–44.

(15) Delisle B, Calinescu C, Mateescu MA, Fairbrother JM, Nadeau É. Oral immunization with F4 fimbriae and CpG formulated with carboxymethyl starch enhances F4-specific mucosal immune response and modulates Th1 and Th2 cytokines in weaned pigs. J Pharm Pharmaceut Sci 2012; 15: 642–56.

(16) Sauerwein H, Schmitz S, Hiss S. Effects of dietary application of a yeast cell wall extract on innate and acquired immunity, on oxidative status and growth performance in weanling piglets and on the ileal epithelium in fattened pigs. J Anim Physiol Anim Nutr 2007; 91: 369–80.

(17) Villena J, Suzuki R, Fuije H, et al. Immunobiotic Lactobacillus jensenii modulates toll-like receptor 4-induced inflammatory response via negative regulation in porcine antigen presenting cells. Clin. Vaccine Immunol 2012; 19: 1038–53.

(18) Tsukida K, Takahashi T, Iida H, et al. Immunoregulatory effects triggered by immunobiotic Lactobacillus jensenii TL2937 strain involve efficient phagocytosis in porcine antigen presenting cells. BMC Immunol 2016; 17: e21 (12 pp). https://bmcimmunol.biomedcentral.com/articles/10.1186/s12865-016-0160-1

(19) Valpotić H, Samardžija M, Terzić S, et al. Effect of mannan oligosaccharide supplementation on blood and intestinal immune cells, bacteria numbers and performance in weaned pigs. Acta Vet Brno 2016; 85: 267–76.

(20) Valpotic H, Terzic S, Vince S, et al. Infeed supplementation of clinoptilolite favourably modulates intestinal and systemic immunity and some production parameters in weaned pigs. Vet Med 2016; 61: 317–27.

(21) Å ver L, Trutin-Ostović K, ŽubÄić D, et al. Porcine gut T, B and null/γ δ TCR+ cell quantification in the protective immunity to fimbrial/toxin antigens of Escherichia coli. Period Biol 1996; 98: 473–8.

(22) Vijtiuk N, Šver L, Lacković G, Popović M, Božić F, Valpotić I. Intestinal immune response of weaned pigs experimentally vaccinated with F4ac+ non-enterotoxigenic strains of Escherichia coli. Acta Vet Brno 2005; 74: 595–601.

(23) Valpotić H, Šuran J, Prevendar Crnić A, et al. Stimulation by levamisole of cel-mediated immunity in weaned pigs. Ital J Anim Sci 2009; 8: 122–4.

(24) Valpotić H, Mršić G, Gršković B, et al. Effect of polyoxyethylene and polyoxypropylene nonionic block copolymers on performance and recruitment of immune cell subsets in weaned pigs. Acta Vet Scand 2013; 55: 54–62.

(25) Valpotić H, Šperanda M, Kovšca-Janjatović A, et al. Levamisole stimulates proliferation of circulating and intestinal immune cell subsets, gut health and performance in weaned pigs. Can J Anim Sci 2014; 94: 43–53.

(26) Kovšca-Janjatović A, Lacković G, Božić F, et al. Histomorphometric characteristics of immune cells in small intestine of pigs perorally immunized with vaccine candidate F18ac+ nonenterotoxigenic E. coli strain. Eur J Histochem 2009; 53: 189–98.

(27) Kovšca Janjatović A, Lacković G, Božić F, et al. Histomorphometric evaluation of intestinal cellular immune responses in pigs immunized with live oral F4ac+ nonenterotoxigenic E. coli vaccine against postweaning colibacillosis. Eur J Histochem 2010; 54: 18–24.

(28) Valpotić H, Kovšca Janjatović A, Lacković G, et al. Increased number of intestinal villous M cells in levamisole-pretreated weaned pigs experimentally infected with F4ac+ enterotoxigenic Escherichia coli strain. Eur J Histochem 2010; 54: 88–91.

(29) Valpotić H, Barić-Rafaj R, Mrljak V, et al. The influence of immune modulation with levamisole and polyoxyethylene-polyoxypropylene copolymers on hematological and biochemical parameters and intestinal histomorphology of weaned pigs. Vet Arh 2016; 86: 667–84.

(30) Terzić S, Šver L, Valpotić I, Lojkić M, et al. Immunophenotyping of leukocyte subsets in peripheral blood and palatine tonsils of prefattening pigs. Vet Rec Commun 2002; 26: 273–83.

(31) Valpotić I, Vijtiuk N, Trutin-Ostović K, Lacković G. Identification and distribution of CD+ T cell subsets in porcine gut following experimental infection with F4ac+ enterotoxigenic Escherichia coli (ETEC) or non-ETEC strains. Reg Immunol 1994; 6: 387–90.

(32) Zuckermann FA, Gaskins HR. Distribution of porcine CD4/CD8 double-positive T lymphocytes in mucosa-associated lymphoid tissues. Immunology 1996; 87: 493–9.

(33) Zuckermann FA, Husmann RJ. Functional and phenotypic analysis of porcine peripheral blood CD4/CD8 double-positive T cells. Immunology 1996; 87: 500–12.

(34) Pantazis EG, Kinker WT. Assessment of blood leukocyte microbial killing by using a new fluorochrome microassay. J Reticuloendothel Soc 1979; 26: 155–70.

(35) Pomorska-Mól M, Kwit K, Markowska-Daniel I. Major acute phase proteins in pig serum from birth to slaughter. Bull Vet Inst Pulawy 2012; 56: 553–7.

(36) Chen HH, Lin JH, Fung HP, et al. Serum acute phase proteins and swine health status. Can J Vet Res 2003; 67: 283–90.

(37) Murata H, Shimada N, Yoshioka M. Current research on acute phase proteins in veterinary diagnosis: an overview. Vet J 2004; 168: 28–40.

(38) Parra MD, Fuentes P, Tecles F, et al. Porcine acute phase protein concentrations in different diseases in field conditions. J Vet Med B 2006; 53: 488–93.

(39) Pomorska-Mol M, Krzysztof K, Pejsak Z, Markowska-Daniel I. Analysis of the acute-phase protein responses in pigs to clinical and subclinical infection with H3N2 swine influenza virus. Influenza Other Respir Viruses 2014; 8: 228–34.

(40) Du Clos TW, Mold C. The role of C-reactive protein in the resolution of bacterial infection. Curr Opin Infect Dis 2001; 14: 289–93.

(41) Božić F, Mrljak V. Levamisole modulates the numbers and phagocytic functions of leukocytes in weaned pigs vaccinated with non-enterotoxigenic F4ac+ Escherichia coli. Prax Vet 2001; 49: 21–30.

(42) Suda Y, Villena J, Takahashi Y, et al. Immunobiotic Lactobacillus jensenii as immune-health promoting factor to improve growth performance and productivity in post-weaning pigs. BMC Immunol 2014; 15: e24 (18 pp). https://bmcimmunol.biomedcentral.com/articles/10.1186/1471-2172-15-24

(43) Zuckermann FA. Extrathymic CD4/CD8 double positive T cells. Vet Immunol Immunopathol 1999; 72: 55–66.

(44) Zuckermann FA, Pescovitz MD, Aasted B, et al. Report on the analyses of mAb reactive with porcine CD8 for the second international swine CD workshop. Vet Immunol Immunopathol 1998; 60: 291–303.

(45) Božić F, Banović F, Šuran J, Prevendar-Crnić A. Adjuvant activity of levamisole for experimental F18ac+ Escherichia coli oral vaccine against porcine post-weaning colibacillosis. Vet Arh 2011; 81: 199–209.




DOI: https://doi.org/10.26873/SVR-397-2017

Refbacks

  • There are currently no refbacks.


SLOVENIAN VETERINARY RESEARCH, Veterinary Faculty
Our journal is indexed in:
Science Citation Index Expanded, Journal Citation Reports/Science Edition, Agris, Biomedicina Slovenica, CAB Abstracts, IVSI Urlich’s International Periodicals Directory
Gerbičeva 60, SI-1000 Ljubljana, Slovenia, T: +386 (0)1 47 79 100, F: +386 (0)1 28 32 243, E: slovetres@vf.uni-lj.si
Published by computing.si