In vitro cellular responses to Neospora caninum glycosylphosphatidylinositols depend on the host origin of antigen presenting cells
2019
Debare, Héloïse | Schmidt, Jörg | Moiré, Nathalie | Ducournau, Céline | Acosta Paguay, Yoshuá D. | Schwarz, Ralph T. | Dimier-Poisson, Isabelle | Debierre-Grockiego, Françoise | Infectiologie et Santé Publique (UMR ISP) ; Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT) | Philipps Universität Marburg = Philipps University of Marburg | Universidad de las Fuerzas Armadas ESPE ; Partenaires INRAE | Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF) ; Université de Lille-Centre National de la Recherche Scientifique (CNRS) | Deutsche Forschungsgemeinschaft ; Institute for Virology of Marburg ; University of Tours ; INRA ; Region Centre Val de Loire ; bilateral programme PHC PROCOPE 33324XA of EGIDE/DAAD
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Show more [+] Less [-]English. Neosporosis due to Neospora caninum causes abortions in farm animals such as cattle. No treatment and vaccine exist to fight this disease, responsible for considerable economic losses. It is thus important to better understand the immune responses occurring during the pathogenesis to control them in a global strategy against the parasite. In this context, we studied the roles of N. caninum glycosylphosphatidylinositols (GPIs), glycolipids defined as toxins in the related parasite Plasmodium falciparum. We demonstrated for the first time that GPIs could be excreted in the supernatant of N. caninum culture and trigger cell signalling through the Toll-like receptors 2 and 4. In addition, antibodies specific to N. caninum GPIs were detected in the serum of infected mice. As shown for other protozoan diseases, they could play a role in neutralizing GPIs. N. caninum GPIs were able to induce the production of tumour necrosis factor-α, interleukin(IL)-1β and IL-12 cytokines by murine macrophages and dendritic cells. Furthermore, GPIs significantly reduced expression of major histocompatibility complex (MHC) molecules of class I on murine dendritic cells. In contrast to murine cells, bovine blood mononuclear cells produced increased levels of IFN-γ and IL-10, but reduced levels of IL-12p40 in response to GPIs. On these bovine cells, GPI had the tendency to up-regulate MHC class I, but to down-regulate MHC class II. Altogether, these results suggest that N. caninum GPIs might differentially participate in the responses of antigen presenting cells induced by the whole parasite in mouse models of neosporosis and in the natural cattle host.
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