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Manipulation of mitogen‐activated protein kinase/nuclear factor‐κB‐signaling cascades during intracellular Toxoplasma gondii infection
Author(s) -
Denkers Eric Y.,
Butcher Barbara A.,
Del Rio Laura,
Kim Leesun
Publication year - 2004
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.0105-2896.2004.00180.x
Subject(s) - biology , proinflammatory cytokine , toxoplasma gondii , mapk/erk pathway , microbiology and biotechnology , signal transduction , tlr4 , protein kinase a , chemokine , kinase , tumor necrosis factor alpha , mitogen activated protein kinase , immunology , inflammation , antibody
Summary: The intracellular protozoan Toxoplasma gondii exerts profound effects on nuclear factor‐κB (NF‐κB)‐ and mitogen‐activated protein kinase (MAPK)‐signaling cascades in macrophages. During early infection, nuclear translocation of NF‐κB 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‐α and IL‐12 (IL‐12) that likely reflects interference with NF‐κB‐ 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.