Recognition by toll-like receptor 2 induces antigen-presenting cell activation and Th1 programming during infection by Neospora caninum

Author(s)

Mineo, Tiago W. P. ^{[1, 2]} ; Oliveira, Carlo J. F. ^[3] ; Gutierrez, Fredy R. S. ; Silva, Joao S.

Affiliation

^[1] Univ Fed Uberlandia, Inst Biomed Sci, BR-38400 Uberlandia, MG - Brazil

^[2] Univ Sao Paulo, FMRP, Sch Med Ribeirao Preto, Dept Biochem & Immunol, Immunoparasitol Lab, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 - USA

• Document type: Journal article
• Source: Immunology and Cell Biology; v. 88, n. 8, p. 825-833, NOV-DEC 2010.
• Web of Science Citations: 28

Abstract

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-gamma: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. Immunology and Cell Biology (2010) 88, 825-833; doi:10.1038/icb.2010.52; published online 20 April 2010 (AU)

• FAPESP's process: 06/06803-4 - The role of Toll like receptors in the imune response towards Neospora caninum
• Grantee: Tiago Wilson Patriarca Mineo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral