Conjugated linoleic acid modifies transcriptional cytokine profile and induces early specific secretory IgA response in Giardia lamblia infected mice

Objective(s): Adaptive immunity is crucial in controlling Giardia lamblia infection in the intestinal mucosa, and some dietary lipids may improve mucosal immune function. The aim of this study was to evaluate conjugated linoleic acid (CLA) on the Th17/Treg response and secretory IgA production in a model of giardiasis infection. Materials and Methods: C3H/HeN male mice were infected with 5×106 G. lamblia trophozoites (GS/M-83-H7, ATCC collection). Mice were assigned randomly to experimental and control groups. CLA was administered to the experimental group and phosphate-buffered saline (PBS) was given to the control group. Parasite load kinetics was determined. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate IgA and cytokines. Nuclear transcription factors and cytokines were measured by RT-qPCR, and histology of small bowel cells was evaluated. Results: CLA administration reduced the parasite load (P<0.05) and increased early Giardia-specific secretory IgA production. CLA also increased the expression of interleukin-10, transforming growth factor (TGF)-β, and inducible nitric oxide synthase (iNOS) (P<0.05), while infection elevated the expression of Foxp3, with a peak at 40 days post-infection (P<0.05). There were no pathological changes in the colonic mucosa due to infection or treatment. Thus, CLA stimulated mucosal immunity and enhanced the humoral response against G. lamblia, not only for early infection control but also to promote regulatory cytokine production at 40 dpi, restoring the intestinal balance after parasite elimination. Conclusion: Our findings reveal novel anti-parasitic effects through the immune-modulatory activity of CLA against the intestinal parasite G. lamblia.

[1]  S. Solaymani-Mohammadi.  Mucosal Defense Against Giardia at the Intestinal Epithelial Cell Interface , 2022, Frontiers in Immunology.

[2]  G. Torres-Hernández,et al.  Immune and parasitic response to conjugated linoleic acid in the diet of pelibuey sheep infected with gastrointestinal nematodes , 2021, Italian Journal of Animal Science.

[3]  Guillermo López Cervantes,et al.  Conjugated linoleic acid enhances intestinal mucosal innate immunity against parasite Giardia lamblia in a murine model , 2018 .

[4]  L. Eckmann,et al.  IL-17A promotes protective IgA responses and expression of other potential effectors against the lumen-dwelling enteric parasite Giardia. , 2015, Experimental parasitology.

[5]  H. Astiazarán-García,et al.  Host defences against Giardia lamblia , 2015, Parasite immunology.

[6]  B. Bernstein,et al.  Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation , 2015, Nature.

[7]  A. Burgara-Estrella,et al.  Dietary conjugated linoleic acid and its effect on immune response in pigs infected with the porcine reproductive and respiratory syndrome virus. , 2015, Research in veterinary science.

[8]  M. Arafa,et al.  Natural regulatory T cells in some parasitic diseases , 2014 .

[9]  H. Roche,et al.  Conjugated linoleic acid suppresses dendritic cell activation and subsequent Th17 responses. , 2014, The Journal of nutritional biochemistry.

[10]  L. Fleurisse,et al.  Antibody and cytokine responses to Giardia excretory/secretory proteins in Giardia intestinalis-infected BALB/c mice , 2014, Parasitology Research.

[11]  K. De Bosscher,et al.  Giardia muris Infection in Mice Is Associated with a Protective Interleukin 17A Response and Induction of Peroxisome Proliferator-Activated Receptor Alpha , 2014, Infection and Immunity.

[12]  Y. Ni,et al.  Persistent gut barrier damage and commensal bacterial influx following eradication of Giardia infection in mice , 2013, Gut Pathogens.

[13]  L. O’Neill,et al.  Conjugated linoleic acid suppresses IRF3 activation via modulation of CD14. , 2013, The Journal of nutritional biochemistry.

[14]  J. Mehta,et al.  Regulation of MSR-1 and CD36 in macrophages by LOX-1 mediated through PPAR-γ. , 2013, Biochemical and biophysical research communications.

[15]  D. Fitzgerald,et al.  IL‐10 mediates the immunoregulatory response in conjugated linoleic acid‐induced regression of atherosclerosis , 2013, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[16]  J. Lundberg,et al.  Dietary conjugated linoleic acid activates PPARγ and the intestinal trefoil factor in SW480 cells and mice with dextran sulfate sodium-induced colitis. , 2012, The Journal of nutrition.

[17]  J. Bassaganya-Riera,et al.  Immunoregulatory Mechanisms Underlying Prevention of Colitis-Associated Colorectal Cancer by Probiotic Bacteria , 2012, PloS one.

[18]  Yuan-Lu Cui,et al.  Dietary Blue Pigments Derived from Genipin, Attenuate Inflammation by Inhibiting LPS-Induced iNOS and COX-2 Expression via the NF-κB Inactivation , 2012, PloS one.

[19]  T. Nash,et al.  Giardia duodenalis: dendritic cell defects in IL-6 deficient mice contribute to susceptibility to intestinal infection. , 2012, Experimental parasitology.

[20]  Q. Fu,et al.  The Treg/Th17 Imbalance in Toxoplasma gondii‐Infected Pregnant Mice , 2012, American journal of reproductive immunology.

[21]  F. Gillin,et al.  Α1-giardin based live heterologous vaccine protects against Giardia lamblia infection in a murine model. , 2011, Vaccine.

[22]  E. Jeung,et al.  Trans-10, cis-12-conjugated linoleic acid modulates NF-κB activation and TNF-α production in porcine peripheral blood mononuclear cells via a PPARγ-dependent pathway. , 2011, The British journal of nutrition.

[23]  F. Pérez-Cano,et al.  Enhancement of antibody synthesis in rats by feeding cis-9,trans-11 conjugated linoleic acid during early life. , 2011, The Journal of nutritional biochemistry.

[24]  S. Singer,et al.  Giardia duodenalis: the double-edged sword of immune responses in giardiasis. , 2010, Experimental parasitology.

[25]  M. Cury,et al.  Giardia duodenalis: kinetics of cyst elimination and the systemic humoral and intestinal secretory immune responses in gerbils (Meriones unguiculatus) experimentally infected. , 2010, Experimental parasitology.

[26]  F. Hayden,et al.  Effects of dietary supplementation with conjugated linoleic acid on experimental human rhinovirus infection and illness , 2009, Antiviral therapy.

[27]  F. Pérez-Cano,et al.  Long-term feeding of the cis-9,trans-11 isomer of conjugated linoleic acid reinforces the specific immune response in rats. , 2009, The Journal of nutrition.

[28]  K. Fritsche.  Fatty acids as modulators of the immune response. , 2006, Annual review of nutrition.

[29]  H. Astiazarán-García,et al.  Giardia lamblia infection induces different secretory and systemic antibody responses in mice , 2005, Parasite immunology.

[30]  H. Goldman,et al.  Chronic diarrhea associated with hypogammaglobulinemia and enteropathy in infants and children , 1985, Digestive Diseases and Sciences.

[31]  H. Roche,et al.  Conjugated Linoleic Acid Suppresses NF- B Activation and IL-12 Production in Dendritic Cells through ERK-Mediated IL-10 Induction , 2005 .

[32]  J. Bassaganya-Riera,et al.  Immunomodulatory properties of conjugated linoleic acid. , 2004, The American journal of clinical nutrition.

[33]  S. Czinn,et al.  Bacterial Probiotic Modulation of Dendritic Cells , 2004, Infection and Immunity.

[34]  P. Halbur,et al.  Conjugated linoleic acid ameliorates viral infectivity in a pig model of virally induced immunosuppression. , 2003, The Journal of nutrition.

[35]  L. Eckmann.  Mucosal defences against Giardia , 2003, Parasite immunology.

[36]  A. Rudensky,et al.  Foxp3 programs the development and function of CD4+CD25+ regulatory T cells , 2003, Nature Immunology.

[37]  Koji Yamada,et al.  Immunoglobulin and cytokine production from spleen lymphocytes is modulated in C57BL/6J mice by dietary cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid. , 2003, The Journal of nutrition.

[38]  M. Belury,et al.  Conjugated linoleic acid is an activator and ligand for peroxisome proliferator-activated receptor-gamma (PPARγ) , 2002 .

[39]  D. Lloyd,et al.  Current Trends in Research into the Waterborne Parasite Giardia , 2002, Critical reviews in microbiology.

[40]  R. D. Adam,et al.  Biology of Giardia lamblia , 2001, Clinical Microbiology Reviews.

[41]  M. Sugano,et al.  Dietary Conjugated Linoleic Acid Increases Immunoglobulin Productivity of Sprague-Dawley Rat Spleen Lymphocytes , 2000, Bioscience, biotechnology, and biochemistry.

[42]  G. Faubert.  Immune Response to Giardia duodenalis , 2000, Clinical Microbiology Reviews.

[43]  M. Sugano,et al.  Conjugated linoleic acid modulates tissue levels of chemical mediators and immunoglobulins in rats , 1998, Lipids.

[44]  Y. Ortega,et al.  Giardia: overview and update. , 1997, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[45]  T. Nash,et al.  Giardia lamblia infections in adult mice , 1994, Infection and immunity.

[46]  M. Pariza,et al.  Dietary sources of conjugated dienoic isomers of linoleic acid, a newly recognized class of anticarcinogens , 1992 .

[47]  D. Snider,et al.  Chronic giardiasis in B-cell-deficient mice expressing the xid gene , 1988, Infection and immunity.

[48]  D. Keister.  Axenic culture of Giardia lamblia in TYI-S-33 medium supplemented with bile. , 1983, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[49]  M. Iuchtman.  [The treatment of giardiasis]. , 1965, Hospital.

[50]  Thomas D. Schmittgen,et al.  Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2 2 DD C T Method , 2022 .