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Diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii.

Publication ,  Journal Article
Liu, C-H; Machado, FS; Guo, R; Nichols, KE; Burks, AW; Aliberti, JC; Zhong, X-P
Published in: J Exp Med
April 16, 2007

Mammalian Toll-like receptors (TLRs) recognize microbial pathogen-associated molecular patterns and are critical for innate immunity against microbial infection. Diacylglycerol (DAG) kinases (DGKs) regulate the intracellular levels of two important second messengers involved in signaling from many surface receptors by converting DAG to phosphatidic acid (PA). We demonstrate that the zeta isoform of the DGK family (DGKzeta) is expressed in macrophages (Mphi) and dendritic cells. DGKzeta deficiency results in impaired interleukin (IL) 12 and tumor necrosis factor alpha production following TLR stimulation in vitro and in vivo, increased resistance to endotoxin shock, and enhanced susceptibility to Toxoplasma gondii infection. We further show that DGKzeta negatively controls the phosphatidylinositol 3-kinase (PI3K)-Akt pathway and that inhibition of PI3K activity or treatment with PA can restore lipopolysaccharide-induced IL-12 production by DGKzeta-deficient Mphi. Collectively, our data provide the first genetic evidence that an enzyme involved in DAG/PA metabolism plays an important role in innate immunity and indicate that DGKzeta promotes TLR responses via a pathway involving inhibition of PI3K.

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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

April 16, 2007

Volume

204

Issue

4

Start / End Page

781 / 792

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Toxoplasmosis
  • Toxoplasma
  • Toll-Like Receptors
  • Th1 Cells
  • Survival Rate
  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Phosphatidic Acids
 

Citation

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Liu, C.-H., Machado, F. S., Guo, R., Nichols, K. E., Burks, A. W., Aliberti, J. C., & Zhong, X.-P. (2007). Diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii. J Exp Med, 204(4), 781–792. https://doi.org/10.1084/jem.20061856
Liu, Cheng-Hu, Fabiana S. Machado, Rishu Guo, Kim E. Nichols, A Wesley Burks, Julio C. Aliberti, and Xiao-Ping Zhong. “Diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii.J Exp Med 204, no. 4 (April 16, 2007): 781–92. https://doi.org/10.1084/jem.20061856.
Liu C-H, Machado FS, Guo R, Nichols KE, Burks AW, Aliberti JC, et al. Diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii. J Exp Med. 2007 Apr 16;204(4):781–92.
Liu, Cheng-Hu, et al. “Diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii.J Exp Med, vol. 204, no. 4, Apr. 2007, pp. 781–92. Pubmed, doi:10.1084/jem.20061856.
Liu C-H, Machado FS, Guo R, Nichols KE, Burks AW, Aliberti JC, Zhong X-P. Diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii. J Exp Med. 2007 Apr 16;204(4):781–792.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

April 16, 2007

Volume

204

Issue

4

Start / End Page

781 / 792

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Toxoplasmosis
  • Toxoplasma
  • Toll-Like Receptors
  • Th1 Cells
  • Survival Rate
  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Phosphatidic Acids