Innate and acquired immunity intersect in a global view of the acute-phase response

Recognition of stereotypic chemical patterns by sentinel cells of the innate immune system provokes a transient deviation from homeostasis, the acute-phase response (APR). Although APR effectors have been identified individually, the complexity of the response suggested that emergent properties would be uncovered by a more comprehensive examination. Our global assessment revealed that ≈7% of genes in the mouse are mobilized in the hepatic APR to endotoxin. Extensive metabolic adjustments include suppression of pathways for cholesterol, fatty acid, and phospholipid synthesis. Increased expression of genes for innate defense was accompanied by coordinate induction of the MHC class I antigen presentation machinery, illustrating an intersection between innate and adaptive immunity.

[1]  C. Scriver,et al.  The Metabolic and Molecular Bases of Inherited Disease, 8th Edition 2001 , 2001, Journal of Inherited Metabolic Disease.

[2]  U. Boehm,et al.  Regulation of the expression of mouse TAP-associated glycoprotein (tapasin) by cytokines. , 2002, Immunology letters.

[3]  Charles A. Janeway,et al.  Decoding the Patterns of Self and Nonself by the Innate Immune System , 2002, Science.

[4]  Daniel Nathans,et al.  Specific Ablation of Stat3β Distorts the Pattern of Stat3-Responsive Gene Expression and Impairs Recovery from Endotoxic Shock , 2002, Cell.

[5]  Ruslan Medzhitov,et al.  Toll-like receptors and innate immunity , 2001, Nature Reviews Immunology.

[6]  L. Gerwick,et al.  The acute phase response and innate immunity of fish. , 2001, Developmental and comparative immunology.

[7]  N. Kadowaki,et al.  Subsets of Human Dendritic Cell Precursors Express Different Toll-like Receptors and Respond to Different Microbial Antigens , 2001, The Journal of experimental medicine.

[8]  S. Akira,et al.  Toll-like receptors control activation of adaptive immune responses , 2001, Nature Immunology.

[9]  K. Feingold,et al.  In Vivo and in Vitro Regulation of Sterol 27-Hydroxylase in the Liver during the Acute Phase Response , 2001, The Journal of Biological Chemistry.

[10]  F. Leithäuser,et al.  Activating Immunity in the Liver. I. Liver Dendritic Cells (but Not Hepatocytes) Are Potent Activators of IFN-γ Release by Liver NKT Cells1 , 2001, The Journal of Immunology.

[11]  F. Azzaroli,et al.  Antigen Presentation by Liver Cells Controls Intrahepatic T Cell Trapping, Whereas Bone Marrow-Derived Cells Preferentially Promote Intrahepatic T Cell Apoptosis1 , 2001, The Journal of Immunology.

[12]  P. Lehner,et al.  Mobilization of MHC class I molecules from late endosomes to the cell surface following activation of CD34-derived human Langerhans cells , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Z. Kmieć,et al.  Introduction — Morphology of the Liver Lobule , 2001 .

[14]  G. Stark,et al.  How Stat1 mediates constitutive gene expression: a complex of unphosphorylated Stat1 and IRF1 supports transcription of the LMP2 gene , 2000, The EMBO journal.

[15]  P. D. Hodgson,et al.  Posttranscriptional Inhibition of Class I Major Histocompatibility Complex Presentation on Hepatocytes and Lymphoid Cells in Chronic Woodchuck Hepatitis Virus Infection , 2000, Journal of Virology.

[16]  F. Sallusto,et al.  Dendritic cells up‐regulate immunoproteasomes and the proteasome regulator PA28 during maturation , 1999, European journal of immunology.

[17]  K. Feingold,et al.  Regulation of Glycosphingolipid Metabolism in Liver during the Acute Phase Response* , 1999, The Journal of Biological Chemistry.

[18]  S. Akira,et al.  Unresponsiveness of MyD88-deficient mice to endotoxin. , 1999, Immunity.

[19]  I. Kushner,et al.  Acute-phase proteins and other systemic responses to inflammation. , 1999, The New England journal of medicine.

[20]  K. Feingold,et al.  Endotoxin and interleukin-1 decrease hepatic lipase mRNA levels. , 1999, Atherosclerosis.

[21]  H. Liebich,et al.  Upregulation of cholesterol synthesis after acute myocardial infarction--is cholesterol a positive acute phase reactant? , 1999, Atherosclerosis.

[22]  R. Ross,et al.  Atherosclerosis is an inflammatory disease. , 1998, American heart journal.

[23]  G. Ramadori,et al.  Cytokines and the hepatic acute phase response , 1997, The Journal of pathology.

[24]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[25]  J. Altman,et al.  Characteristics of virus-specific CD8(+) T cells in the liver during the control and resolution phases of influenza pneumonia. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[26]  K. Feingold,et al.  Endotoxin and cytokines increase hepatic sphingolipid biosynthesis and produce lipoproteins enriched in ceramides and sphingomyelin. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[27]  D. Russell,et al.  Two 7α‐hydroxylase enzymes in bile acid biosynthesis , 1998 .

[28]  K. Feingold,et al.  Endotoxin, tumor necrosis factor, and interleukin-1 decrease hepatic squalene synthase activity, protein, and mRNA levels in Syrian hamsters. , 1997, Journal of lipid research.

[29]  C. Janeway,et al.  A human homologue of the Drosophila Toll protein signals activation of adaptive immunity , 1997, Nature.

[30]  H. Ruffner,et al.  Regulation of LMP2 and TAP1 genes by IRF-1 explains the paucity of CD8+ T cells in IRF-1-/- mice. , 1996, Immunity.

[31]  W. Min,et al.  Kinetically coordinated induction of TAP1 and HLA class I by IFN-gamma: the rapid induction of TAP1 by IFN-gamma is mediated by Stat1 alpha. , 1996, Journal of immunology.

[32]  K. Feingold,et al.  Endotoxin, TNF, and IL-1 decrease cholesterol 7 alpha-hydroxylase mRNA levels and activity. , 1996, Journal of lipid research.

[33]  K. Feingold,et al.  Effects of endotoxin on lipid metabolism. , 1995, Biochemical Society transactions.

[34]  K. Feingold,et al.  Discordant regulation of proteins of cholesterol metabolism during the acute phase response. , 1995, Journal of lipid research.

[35]  G. Su,et al.  Role of lipopolysaccharide (LPS), interleukin-1, interleukin-6, tumor necrosis factor, and dexamethasone in regulation of LPS-binding protein expression in normal hepatocytes and hepatocytes from LPS-treated rats , 1995, Infection and immunity.

[36]  R. Flavell,et al.  The liver eliminates T cells undergoing antigen-triggered apoptosis in vivo. , 1994, Immunity.

[37]  P. A. Peterson,et al.  Displacement of housekeeping proteasome subunits by MHC‐encoded LMPs: a newly discovered mechanism for modulating the multicatalytic proteinase complex. , 1994, The EMBO journal.

[38]  M. Takashina,et al.  Replacement of proteasome subunits X and Y by LMP7 and LMP2 induced by interferon‐γ for acquirement of the functional diversity responsible for antigen processing , 1994, FEBS letters.

[39]  P M Kloetzel,et al.  Interferon gamma stimulation modulates the proteolytic activity and cleavage site preference of 20S mouse proteasomes , 1994, The Journal of experimental medicine.

[40]  J. Taylor,et al.  Effect of endotoxin on cholesterol biosynthesis and distribution in serum lipoproteins in Syrian hamsters. , 1993, Journal of lipid research.

[41]  T. Starzl,et al.  Purine nucleoside phosphorylase: A new marker for free oxygen radical injury to the endothelial cell , 1990, Hepatology.

[42]  M. Frank,et al.  Phagocytosis of target particles bearing C3b-IgG covalent complexes by human monocytes and polymorphonuclear leucocytes. , 1987, Immunology.

[43]  R. Stearman,et al.  Transcriptional regulation of serum amyloid A gene expression. , 1986, The Journal of biological chemistry.

[44]  P. Le,et al.  Induction and regulation by monokines of hepatic synthesis of the mouse serum amyloid P-component (SAP). , 1986, Journal of immunology.