Publication Date:
2007-06-16
Description:
The inflammatory toxicity of lipopolysaccharide (LPS), a component of bacterial cell walls, is driven by the adaptor proteins myeloid differentiation factor 88 (MyD88) and Toll-interleukin 1 receptor domain-containing adapter inducing interferon-beta (TRIF), which together mediate signaling by the endotoxin receptor Toll-like receptor 4 (TLR4). Monophosphoryl lipid A (MPLA) is a low-toxicity derivative of LPS with useful immunostimulatory properties, which is nearing regulatory approval for use as a human vaccine adjuvant. We report here that, in mice, the low toxicity of MPLA's adjuvant function is associated with a bias toward TRIF signaling, which we suggest is likely caused by the active suppression, rather than passive loss, of proinflammatory activity of this LPS derivative. This finding may have important implications for the development of future vaccine adjuvants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mata-Haro, Veronica -- Cekic, Caglar -- Martin, Michael -- Chilton, Paula M -- Casella, Carolyn R -- Mitchell, Thomas C -- AI059023/AI/NIAID NIH HHS/ -- AI51377/AI/NIAID NIH HHS/ -- K02 AI059023/AI/NIAID NIH HHS/ -- R01 AI051377/AI/NIAID NIH HHS/ -- R01 AI071047/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Jun 15;316(5831):1628-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cellular Therapeutics, University of Louisville, 570 South Preston Street, Louisville, KY 40202, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17569868" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Vesicular Transport/*metabolism
;
*Adjuvants, Immunologic/administration & dosage/toxicity
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Adoptive Transfer
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Animals
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Cytokines/biosynthesis
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Immunization
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Lipid A/administration & dosage/*analogs & derivatives/immunology/toxicity
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Lipopolysaccharides/immunology
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Lymphocyte Activation
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Macrophages/immunology
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Mice
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Mice, Inbred C57BL
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Monocytes/immunology
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Myeloid Differentiation Factor 88/metabolism
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Oligonucleotide Array Sequence Analysis
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Ovalbumin/immunology
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Phosphatidylinositol 3-Kinases/metabolism
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Signal Transduction
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T-Lymphocytes/immunology
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Toll-Like Receptor 4/*agonists/*immunology/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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