Recognition by Toll-like receptor 2 induces antigen-presenting cell activation and Th1 programming during infection by Neospora caninum.
Neospora caninum is an apicomplexan parasite responsible for major economic losses due to abortions in cattle. Toll-like receptors (TLRs) sense specific microbial products and direct downstream signaling pathways in immune cells, linking innate, and adaptive immunity. Here, we analyze the role of TLR2 on innate and adaptive immune responses during N. caninum infection. Inflammatory peritoneal macrophages and bone marrow-derived dendritic cells exposed to N. caninum-soluble antigens presented an upregulated expression of TLR2. Increased receptor expression was correlated to TLR2/MyD88-dependent antigen-presenting cell maturation and pro-inflammatory cytokine production after stimulation by antigens. Impaired innate responses observed after infection of mice genetically deficient for TLR2((-/-)) was followed by downregulation of adaptive T helper 1 (Th1) immunity, represented by diminished parasite-specific CD4(+) and CD8(+) T-cell proliferation, IFN-γ:interleukin (IL)-10 ratio, and IgG subclass synthesis. In parallel, TLR2(-/-) mice presented higher parasite burden than wild-type (WT) mice at acute and chronic stages of infection. These results show that initial recognition of N. caninum by TLR2 participates in the generation of effector immune responses against N. caninum and imply that the receptor may be a target for future prophylactic strategies against neosporosis.
Mineo
Tiago W P
TW
Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil. tiago.mineo@pq.cnpq.br
Oliveira
Carlo J F
CJ
Gutierrez
Fredy R S
FR
Silva
João S
JS
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002417:Cattle; D002454:Cell Differentiation / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D002478:Cells, Cultured; D003048:Coccidiosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018688:Neospora / Q000276:immunology* / Q000472:pathogenicity; D058408:Th1-Th2 Balance; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; D018836:Inflammation Mediators; D051195:Toll-Like Receptor 2