Conjugated linoleic acid enhances intestinal mucosal innate immunity against parasite Giardia lamblia in a murine model

Maricela Montalvo Corral, Lucinda Puebla Clark, Guadalupe López Robles, Itzel Reyes Duarte, Guillermo López Cervantes, Silvia Yolanda Moya Camarena

Abstract


Introduction: Giardia lamblia, a protozoan intestinal parasite is able to evade or suppress defense mechanisms, such as innate response. Antigen presenting cells (APC) like dendritic cells may orchestrate an immune response and support a more effective adaptive defense. Conjugated linoleic acid (CLA), a dietary lipid, has shown biological activity on APC. The aim was to evaluate the effect of CLA in intestinal innate response measuring the frequency of mucosal APC populations in Giardia lamblia murine infection.

Method: The giardiasis infection model was established in C3H/HeN mice (n=32), and parasite load was followed at 0, 2, 6 and 8 days post infection (dpi). APC obtained from small intestine by enzymatic digestion were assessed by flow cytometry. Oral supplementation with CLA (50:50 of cis-9, trans-11-CLA and trans-10, cis-12-CLA isomers) and placebo control begun three days before infection and continued during first week post infection.

Results: Infection kinetics showed a peak of trophozoites at 6 dpi in acute phase. Parasite load was lower in CLA group in comparison with control infected group (p<0.05). Conjugated linoleic acid stimulates innate immune response, percentage of intestinal CD11chiMHC-IIhi increases after 2 dpi, meanwhile CD11chiMHC-IIhiCD103+ APC was higher after three days of CLA supplementation than control (p<0.05). Also, the CD11c+ F4/80+ population shown a percentage increases after 6 and 8 dpi by the effect of treatment and time of infection (p<0.05).

Conclusion: In conclusion CLA increased percentages of small intestine APC phenotypes CD11chiMHCIIhi, CD11chiMHCIIhiCD103+ and CD11c+ F4/80+, and reduced G. lamblia parasitic load. Further studies are needed to elucidate potential mechanisms involved in CLA immunomodulatory effect and its contribution in adaptive immune response.

 


Keywords


conjugated linoleic acid; Giardia lamblia; APC; intestinal innate immunity; murine

Full Text:

PDF

References


Albers, R., van der Wielen, R.P., Brink, E.J., Hendriks, H.F., Dorovska-Taran, V.N., Mohede, I.C. (2003). Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men. Eur J Clin Nutr, 57:595-603.

Balachandar, S., Katyal, A., (2010). Peroxisome proliferator activating receptor (PPAR) in cerebral malaria (CM): a novel target for an additional therapy. Eur J Clin Microbiol Infect Dis, 30: 483-498.

Belosevic, M., Daniels, C.W. (1992). Phagocytosis of Giardia lamblia trophozoites by cytokine-activated macrophages. Clin Exp Immunol, 87 (2): 304–309.

Benjamin, S., Spener. F. (2009). Conjugated linoleic acids as functional food: an insight into their health benefits. Nutr Metab. 6-36.

Boggild, A.K., Krudsood, S., Patel, S.N., Serghides, L., Tangpukdee, N., Katz, K., Wilairatana, P., Liles, W.C., Looareesuwan, S., Kain, K.C. (2009). Use of peroxisome proliferator-activated receptor gamma agonists as adjunctive treatment for Plasmodium falciparum malaria: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis 49, 841-849.

Chen, H., He, Y., Li, W., Zhang, J., (2008). Rosiglitazone prevents murine hepatic fibrosis induced by Schistosoma japonicum. World J Gastroenterol, 14:2905-2911.

Chin, S.F., Liu, W., Storkson, J.M., Ha, Y.L., Pariza, M.W. (1992). Dietary sources of conjugated dienoic isomers of linoleic acid, a newly recognized class of anticarcinogens. J Food Comp and Anal, 5(3):185–197.

Cho, M.H., Kang, J. H., Yang, M.P. (2008). Immunoenhancing effect of trans-10, cis-12 conjugated linoleic acid on the phagocytic capacity and oxidative burst activity of canine peripheral blood phagocytes. Res Vet Sci. doi: 10.1016/j.rvsc.2007.12.005.

Clark, R.B., Bishop-Bailey, D., Estrada-Hernandez, T., Hla, T., Puddington, L., Padula, S.J. (2000). The nuclear receptor PPAR gamma and immunoregulation: PPAR gamma mediates inhibition of helper T cell responses. J Immunol 164, 1364-1371.

Clark, R.B. (2002). The role of PPARs in inflammation and immunity. J Leukoc Biol 71, 388-400.

Daynes, R.A., Jones, D.C.(2002). Emerging roles of PPARs in inflammation and immunity. Nat Rev Immunol 2, 748-759.

Denning, T. L., Wang, Y. C., Patel, S. R., Williams, I. R., Pulendran, B. (2007). Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses. Nat Immunol, 8(10):1086-94.

Drakes, M. L., Czinn, S. J., Blanchard, T. G. (2004). Isolation and purification of colon lamina propia dendritic cells from mice with colitis. 2004. Cytotechnol, 46: 151-161.

Fink, M.Y., Maloney J.G., Singer, S.M. (2018). Myeloid cells in the immune response to Giardia. J Immunol 200 (1 Supplement) 52.12

Fink, M. Y., Singer, S. M. (2017). The intersection of immune responses, microbiota, and pathogenesis in Giardiasis. Trends Parasitol, 33(11): 901–913.

Franco, M. C., Golowczyz, M. A., G. L. De Antoni, P. F. Pérez, M. Humen, M. de L. Serradel. (2013). Administration of kéfir-fermented milk protects mice against Giardia intestinalis infection. J Med Microbiol, 62:1815-22.

Kamda, J. D., Nash, T. E., Singer, S. M. (2012). Giardia duodenalis: dendritic cell defects in IL-6 deficient mice contribute to susceptibility to intestinal infection. Exp Parasitol, 130(3):288-91.

Kang, J. H., Lee, G. S., Jeung, E. B., Yang, M. P. (2007). Trans-10, cis-12-conjugated linoleic acid increases phagocytosis of porcine peripheral blood polymorphonuclear cells in vitro. Br J Nutr, 97(1):117-25.

Kumar, R., Arora, D., Bhatia, A.(2010). Therapeutic Potential Of Bioconverted Conjugated Linoleic Acid In Drug Induced Immuosuppressed And Infective Organism Induced Plasmodium Berghei. Int J Pharm Pharm Sci, 3(1): 212-214.

Lantier, L., Lacroix-Lamandé, S., Potiron, L., Metton, C., Drouet, F., Guesdon, W., Gnahoui-David, A., Le Vern, Y., Deriaud, E., Fenis, A., Rabot, S., Descamps, A., Werts, C., Laurent. F. (2013). Intestinal CD103+ dendritic cells are key player in the innate immune control of Cryptosporidium parvum infection in neonatal mice. PLoS Pathog, 9(12):e1003801.

Langford, T.D., Housley, M.P., Boes, M., Chen, J., Kagnoff, M.F., Gillin, F.D., Eckmann, L. (2002). Central importance of immunoglobulin A in host defense against Giardia spp. Infect Immun 70, 11-18.

Lee, H.Y., Kim, J., Noh, H.J., Kim, H.P., Park, S.J. (2015). Giardia lamblia binding immunoglobulin protein triggers maturation of dendritic cells via activation of TLR4- MyD88-p38 and ERK1/2 MAPKs. Parasite Immunol, 36 (12): 627–646.

Li, L., Li, X., Li, G., Gong, P., Zhang, X., Yang, Z., Li, J. (2018). Mouse macrophages capture and kill Giardia lamblia by means of releasing extracellular trap. Dev Comp Immunol, 88:206-212.

Li, X., Zhang, X., Gong, P., Xia, F., Li, L., Yang, Z., Li, J. (2017). TLR2−/−Mice display decreased severity of Giardiasis via enhanced proinflammatory cytokines production dependent on AKT signal pathway. Front Immunol, 8, 1186.

Li, E., Tako, E., Singer, S.M. 2016. Complement activation by Giardia duodenalis parasites through the lectin pathway Contributes to Mast Cell Responses and Parasite Control. Infection Immunity, 84(4):1092-1099.

Lin, H. H., Stacey, M., Stein-Streilein, J., Gordon, S. (2005). F4/80 the macrophage-specific adhesion-GPCR and its role in immunoregulation. Adv Exp Med Biol, 706:149-156.

Lopez-Romero, G., Quintero, J., Astiazarán-García H., Velázquez, H. (2015). Host defenses against Giardia lamblia. Parasite Immunol, 37:394-406.

Maloney, J., Keselman, A., Li, E., Singer, S.M. (2015). Macrophages expressing arginase 1 and nitric oxide synthase 2 accumulate in the small intestine during Giardia lamblia infection. Microbes Infect, 17:462– 467.

Morrison, H.G., McArthur, A.G., Gillin, F.D., Aley, S.B., Adam, R.D., Olsen, G.J., Best, A.A., Cande, W.Z., Chen, F., Cipriano, M.J., Davids, B.J., Dawson, S.C., Elmendorf, H.G., Hehl, A.B., Holder, M.E., Huse, S.M., Kim, U.U., Lasek-Nesselquist, E., Manning, G., Nigam, A., Nixon, J.E., Palm, D., Passamaneck, N.E., Prabhu, A., Reich, C.I., Reiner, D.S., Samuelson, J., Svard, S.G., Sogin, M.L. (2007). Genomic minimalism in the early diverging intestinal parasite Giardia lamblia. Science 317, 1921-1926.

Moya-Camarena, S. Y., Vanden Heuvel, J. P., Blanchard, S. G., Leesnitzer, L. A., Belury, M. A. (1999). Conjugated linoleic acid is a potent naturally occurring ligand and activator of PPARα. J Lipid Res, 40(8):1426-33.

Muñoz-Cruz, S., Gómez-García, A., Matadamas-Martínez F., Alvarado-Torres, J.A., Meza-Cervantes, P., Arriaga-Pizano, L., Yépez-Mulia, L. (2018). Giardia lamblia: identification of molecules that contribute to direct mast cell activation. Parasitol Res, 117(8):2555-2567.

Norma Oficial Mexicana NOM-062-ZOO-1999. (1999).Especificaciones técnicas para la producción, cuidado y uso de los animales de laboratorio. Estados Unidos Mexicanos. Secretaría de Agricultura, Ganadería, Desarrollo Rural, Pesca y Alimentación.

Ortega, Y.R., Adam, R.D. (1997). Giardia: overview and update. Clin Infect Dis, 25:545-549.

O'Shea, M., Bassaganya-Riera, J., Mohede, I. C. (2004). Immunomodulatory properties of conjugated linoleic acid. Am J Clin Nutr, 79(6):1199S-1206S.

Pabst O., Bernhardt, G. (2010). The puzzle of intestinal lamina propria dendritic cells and macrophages. Eur J immunol, 40:2085-2130.

Patel, S.M., Serghides, L., Smith, T.G., Febbraio, M., Silverstein, R.L., Kurtz, T.W., Pravenec, M., Kain K.C. (2004). CD36 Mediates the Phagocytosis of Plasmodium falciparum–Infected Erythrocytes by Rodent Macrophages. J Infect Dis 189, 204-213.

Ramírez-Santana, C., Perez-Cano, F.J., Castellote, C., Castell, M., Rivero, M., Rodriguez-Palmero, M., Franch, A. (2009). Higher immunoglobulin production in conjugated linoleic acid-supplemented rats during gestation and suckling. Br J Nutr, 102: 858-868.

Ramírez-Santana, C., Castellote, C., Castell, M., Moltó-Puigmartí, C., Rivero, M., Pérez-Cano, F. J., Franch, A. (2010). Enhancement of antibody synthesis in rats by feeding cis-9,trans-11 conjugated linoleic acid during early life. J Nutr Biochem, 22(5):495-50.

Rodrigues, W.F., Camila, B.M., Lazo-Chica, J.E., Napimoga, M.H. (2010). 15d-PGJ2 modulates acute immune responses to Trypanosoma cruzi infection. Mem Inst Oswaldo Cruz, 105, 137-142.

Sampath, H., Ntambi, J.M. (2005). Polyunsaturated fatty acid regulation of genes of lipid metabolism. Annu Rev Nutr, 25, 317-340.

Singer, S.M., Nash, T.E., 2000a. The role of normal flora in Giardia lamblia infections in mice. J Infect Dis 181, 1510-1512.

Singer, S.M., Nash, T.E., 2000b. T-cell-dependent control of acute Giardia lamblia infections in mice. Infect Immun 68, 170-175.

Solaymani-Mohammadi, S., Genkinger, J.M., Loffredo, C.A., Singer, S.M. (2010). A meta-analysis of the effectiveness of albendazole compared with metronidazole as treatments for infections with Giardia duodenalis. PLoS Negl Trop Dis, 4(5):e682.

Solaymani-Mohammadi, S., Singer, S.M. (2010). Giardia duodenalis: the double-edged sword of immune responses in giardiasis. Exp Parasitol, 126, 292-297.

Velazquez, C., Beltran, M., Ontiveros, N., Rascon, L., Figueroa, D. C., Granados, A. J., Hernandez-Martinez, J., Hernandez, J., Astiazaran-Garcia, H. (2005). Giardia lamblia infection induces different secretory and systemic antibody responses in mice. Parasite Immunol, 27(9):351-6.

Zhou, P., Li, E., Zhu, N., Robertson, J., Nash, T., Singer, S.M. (2003). Role of Interleukin-6 in the control of acute and chronic giardia lamblia infections in mice. Infect Immun, 71(3):1566–1568.




DOI: https://doi.org/10.21640/ns.v10i21.1578

Refbacks

  • There are currently no refbacks.


Copyright (c) 2018 Nova Scientia

Scope

Nova Scientia is a multidisciplinary, electronic publication that publishes biannually in the months of May and November; it is published by the Universidad De La Salle Bajío and aims to distribute unpublished and original papers from the different scientific disciplines written by national and international researchers and academics. It does not publish reviews, bibliographical revisions, or professional applications.

Nova Scientia, year 10, issue 20, May – October 2018, is a biannual journal printed by the Universidad De La Salle Bajío, with its address: Av. Universidad 602, Col. Lomas del Campestre, C. P. 37150, León, Gto. México. Phone: (52) 477 214 3900, e-mail: http://nova_scientia.delasalle.edu.mx. Chief editor: Ph.D. Ramiro Rico Martínez. ISSN 2007 - 0705. Copyright for exclusive use No. 04-2008-092518225500/102, Diffusion rights via computer net 04 - 2008 – 121011584800-203 both granted by the Instituto Nacional del Derecho de Autor.

Editor responsible for updating this issue: Direction of Research Department of the Universidad De La Salle Bajío, last updated on May 25th, 2018.