title: Manipulation of mitogen-activated protein kinase/nuclear factor-kappaB-signaling cascades during intracellular Toxoplasma gondii infection.
abstract: The intracellular protozoan Toxoplasma gondii exerts profound effects on nuclear factor-kappaB (NF-kappaB)- and mitogen-activated protein kinase (MAPK)-signaling cascades in macrophages. During early infection, nuclear translocation of NF-kappaB is blocked, and later, the cells display defects in lipopolysaccharide (LPS)-induced MAPK phosphorylation after undergoing initial activation in response to Toxoplasma itself. Infected macrophages that are subjected to triggering through Toll-like receptor 4 (TLR4) with LPS display defective production of tumor necrosis factor-alpha and IL-12 (IL-12) that likely reflects interference with NF-kappaB- and MAPK-signaling cascades. Nevertheless, T. gondii possesses molecules that themselves induce eventual proinflammatory cytokine synthesis. For interleukin-12, this occurs through both myeloid differentiation factor 88-dependent and chemokine receptor CCR5-dependent pathways. The balance between activation and interference with proinflammatory signaling is likely to reflect the need to achieve an appropriate level of immunity that allows the host and parasite to maintain a stable interaction.
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. eyd1@cornell.edu
authors.forename: Eric Y
authors.initials: EY
authors.lastname: Denkers
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Butcher
authors.forename: Laura
authors.initials: L
authors.lastname: Del Rio
authors.forename: Leesun
authors.initials: L
authors.lastname: Kim
mesh_terms: D000818:Animals; D006790:Host-Parasite Interactions; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000469:parasitology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D014122:Toxoplasma / Q000472:pathogenicity*; D014123:Toxoplasmosis / Q000276:immunology / Q000469:parasitology / Q000503:physiopathology
chemical_list: D016328:NF-kappa B; D020928:Mitogen-Activated Protein Kinases