Dectin-1 Compromises Innate Responses and Host Resistance againstNeospora caninumInfection.
Neospora caninumis an intracellular protozoan parasite that has drawn increasing interest due to its association with worldwide repetitive bovine abortions, which cause billionaire losses to the meat and dairy industries annually. Innate immunity plays an important role in infection control, andN. caninumactivates the production of inflammatory mediators through toll-like receptors, NOD-like receptors, and mitogen-activated protein kinase signaling pathways. Advances in the knowledge of initial host-parasite interactions are desirable for the design of control measures against the infection, obliterating its pathogenesis. In that sense, we here aimed to describe the role of the innate C-type lectin receptor Dectin-1 during the infection byN. caninum. With that intent, we observed that the absence of Dectin-1, observed in genetically depleted (Dectin-1-/-) mice or competitively inhibited by an inert agonist [laminarin (LAM)], rescued 50% of the mice infected with lethal doses ofN. caninum. Dectin-1-/-and LAM-treated mice also presented a reduction in the parasite load during acute and chronic phases, associated with decreased inflammatory scores in the central nervous system. Among all the cell phenotypes that migrated to the initial site of infection, dendritic cells and macrophages gained subpopulations with high Dectin-1 surface expression. The impairment of the receptor in these cells led to a decreased parasite burden, as well as augmented production of IL-12p40. We also found that Dectin-1+cells produced less reactive oxygen species (ROS) at the initial site of the infection, while mice deficient in NADPH oxidase isoform 2 (NOX2-/-) were not able to control parasite replication and produce IL-12p40, even upon LAM treatment. Interestingly, the absence of functional Dectin-1 did not alter the susceptibility of mice against closely relatedToxoplasma gondii. In conclusion, the gathered data suggest that Dectin-1 is involved in the parasite-induced downmodulation of ROS, and other key molecules triggered for the control ofN. caninuminfection and are a promising target for future development of protocols intended for intervention against neosporosis.
Laboratory of Immunoparasitology "Dr. Mário Endsfeldz Camargo", Department of Immunology, Institute of Biomedical Sciences, Federal University of Uberlândia , Uberlândia , Brazil.
Murilo Vieira
MV
da Silva
Laboratory of Immunoparasitology "Dr. Mário Endsfeldz Camargo", Department of Immunology, Institute of Biomedical Sciences, Federal University of Uberlândia , Uberlândia , Brazil.
Flávia Batista
FB
Ferreira França
Laboratory of Immunoparasitology "Dr. Mário Endsfeldz Camargo", Department of Immunology, Institute of Biomedical Sciences, Federal University of Uberlândia , Uberlândia , Brazil.
Caroline Martins
CM
Mota
Laboratory of Immunoparasitology "Dr. Mário Endsfeldz Camargo", Department of Immunology, Institute of Biomedical Sciences, Federal University of Uberlândia , Uberlândia , Brazil.
Arlindo Gomes
AG
de Macedo Júnior
Laboratory of Immunoparasitology "Dr. Mário Endsfeldz Camargo", Department of Immunology, Institute of Biomedical Sciences, Federal University of Uberlândia , Uberlândia , Brazil.
Eliézer Lucas Pires
EL
Ramos
Laboratory of Immunoparasitology "Dr. Mário Endsfeldz Camargo", Department of Immunology, Institute of Biomedical Sciences, Federal University of Uberlândia , Uberlândia , Brazil.
Fernanda Maria
FM
Santiago
Laboratory of Immunoparasitology "Dr. Mário Endsfeldz Camargo", Department of Immunology, Institute of Biomedical Sciences, Federal University of Uberlândia , Uberlândia , Brazil.
José Roberto
JR
Mineo
Laboratory of Immunoparasitology "Dr. Mário Endsfeldz Camargo", Department of Immunology, Institute of Biomedical Sciences, Federal University of Uberlândia , Uberlândia , Brazil.
Tiago Wilson Patriarca
TW
Mineo
CLEC7A; IL-12p40; Neospora caninum; Toxoplasma gondii; dendritic cells; laminarin; macrophages; reactive oxygen species