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Summary Aims The objective of this work is to investigate whether Anisakis simplex larval antigens present immunomodulatory properties by the induction of tolerogenic dendritic cells (DCs) from two strains of mice (BALB/c and C57BL/6J). Methods and Results We used mouse bone marrow‐derived DCs. We determined their antigen‐presenting ability by expression of membrane markers (MHC I and MHC II, CD80, CD86) and intracellular expression levels of IL‐10 and IL‐12 cytokines. We also analysed whether stimulation with A simplex larval antigens is enhanced by the co‐administration of the TLR4 and TLR9 agonists [LPS E coli 026B6 and CpG (ODN1826), respectively]. Two differential types of responses were found in the two mouse strains studied: the BALB/c strain showed an acute and inflammatory response, whereas the C57BL/6J mice developed a more discrete and resistant response. This suggests the coexistence of two opposing responses generated by A simplex larval antigens and confirms that the host genetic basis plays a role in the development of a Th2 or Treg response. Conclusion The study of the mechanisms by which Anisakis manipulates the immune response through anti‐inflammatory molecules is of interest not only for the direct application on the development of anthelmintic strategies, but also for the development of new anti‐inflammatory products.

BACKGROUND Anisakis simplex antigens present immunomodulatory properties by the induction of tolerogenic dendritic cells (DCs) in mice. OBJECTIVES To study the capacity of DCs stimulated with A. simplex excretory-secretory (ES) or crude extract (CE) to generate T regs. To investigate in vitro effects of antigens on the metabolic activity of splenocytes induced by LPS or CpG. METHODS Phenotypic and functional characterization of T cells co-cultured with A. simplex-pulsed DCs was performed by flow cytometry. Lymphocyte mitochondrial respiratory activity was estimated by the Alamar Blue ® Assay. FINDINGS In C57BL/6J, CD4 + CD25-Foxp3 + and CD8 + CD25-Foxp3 + populations increased by CE-stimulated-DCs. In BALB/c, CE-stimulated-DCs caused the expansion of CD4 + CD25 + Foxp3 + IL-10+ and CD8 + CD25 + Foxp3 + IL-10+. IFN-γ expression raised in BALB/c CD4 + CD25 + and CD4 + CD25for CE and ES, respectively. ES-stimulated-DCs increased CD4 + CD25 + Foxp3 + and CD8 + CD25-Foxp3 + expression in T cells. The association of ES or CE with LPS produced the increase in splenocyte activity in C57BL/6J. The association of CE with CpG decreased the proliferation caused by CpG in C57BL/6J. MAIN CONCLUSIONS A. simplex increase the frequency of T regs , which in turn produce IL-10 and IFN-γ. The host genetic base is essential in the development of anti-Anisakis immune responses (Th2, Th1, T reg).

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