Heat-shock proteins as activators of the innate immune system.

Abstract Peptides bound or linked to heat-shock proteins (HSPs) of microbial or mammalian origin have been shown to elicit potent antigen-specific immunity. Some members of the HSP family, such as hsp60, hsp70, hsp90 and gp96, are able also to stimulate cells of the innate immune system directly and thus, act as ‘danger'-signaling molecules. This effect is independent of HSP-associated peptides and, in many respects, resembles the effect of lipopolysaccharide (LPS). Here, we discuss the similarities between the responses to HSPs and LPS and also, emphasize that care must be taken when working with preparations of HSPs in experimental settings and interpreting experimental data.

[1]  Z. Darieva,et al.  Effects of exogenous stress protein 70 on the functional properties of human promonocytes through binding to cell surface and internalization. , 1998, Cell stress & chaperones.

[2]  P. Godowski,et al.  Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. , 1999, Science.

[3]  A. Blalock Surgical treatment of pulmonary stenosis. , 1947, Lancet.

[4]  J. Rothman,et al.  Induction of cellular immunity by immunization with novel hybrid peptides complexed to heat shock protein 70. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[5]  N. Bhardwaj,et al.  Primary Tumor Tissue Lysates Are Enriched in Heat Shock Proteins and Induce the Maturation of Human Dendritic Cells1 , 2001, The Journal of Immunology.

[6]  L. Klareskog,et al.  Role of hsp60 during Autoimmune and Bacterial Inflammation , 1991, Immunological reviews.

[7]  Stuart K. Calderwood,et al.  HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine , 2000, Nature Medicine.

[8]  G. Schütz,et al.  Lipopolysaccharide and ceramide docking to CD14 provokes ligand‐specific receptor clustering in rafts , 2001, European journal of immunology.

[9]  A. Marcatili,et al.  Cytokine and adhesion molecule expression in human monocytes and endothelial cells stimulated with bacterial heat shock proteins , 1997, Infection and immunity.

[10]  P. Srivastava,et al.  Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world. , 1998, Immunity.

[11]  P. Matzinger,et al.  An innate sense of danger. , 1998, Seminars in immunology.

[12]  J. Louis,et al.  Mycobacterial heat‐shock proteins as carrier molecules , 1991, European journal of immunology.

[13]  T. Klein,et al.  Bacterial heat shock proteins directly induce cytokine mRNA and interleukin-1 secretion in macrophage cultures , 1994, Infection and immunity.

[14]  M. Machnicki,et al.  Lactoferrin regulates the release of tumour necrosis factor alpha and interleukin 6 in vivo. , 1993, International journal of experimental pathology.

[15]  E. Román,et al.  Synthetic peptides non‐covalently bound to bacterial hsp 70 elicit peptide‐specific T‐cell responses in vivo , 1996, Immunology.

[16]  Stefania Gallucci,et al.  Natural adjuvants: Endogenous activators of dendritic cells , 1999, Nature Medicine.

[17]  P. Srivastava,et al.  CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. , 2001, Immunity.

[18]  S. Kaufmann,et al.  Immune response against heat shock proteins in infectious diseases. , 1999, Immunobiology.

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

[20]  S. Akira,et al.  The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5 , 2001, Nature.

[21]  T. Klein,et al.  Legionella pneumophila heat‐shock protein‐induced increase of interleukin‐1β mRNA involves protein kinase C signalling in macrophages , 1996, Immunology.

[22]  P. Libby,et al.  Cutting Edge: Heat Shock Protein (HSP) 60 Activates the Innate Immune Response: CD14 Is an Essential Receptor for HSP60 Activation of Mononuclear Cells1 , 2000, The Journal of Immunology.

[23]  H. Rammensee,et al.  The heat shock protein gp96 induces maturation of dendritic cells and down‐regulation of its receptor , 2000, European journal of immunology.

[24]  Robert Sim,et al.  The potent bone-resorbing mediator of Actinobacillus actinomycetemcomitans is homologous to the molecular chaperone GroEL. , 1995, The Journal of clinical investigation.

[25]  I. Cohen,et al.  Vaccination against autoimmune mouse diabetes with a T-cell epitope of the human 65-kDa heat shock protein. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[26]  T. Lee,et al.  Mechanisms of stimulation of interleukin-1 beta and tumor necrosis factor-alpha by Mycobacterium tuberculosis components. , 1993, The Journal of clinical investigation.

[27]  F. Breedveld,et al.  SYNOVIAL FLUID T CELL REACTIVITY AGAINST 65 kD HEAT SHOCK PROTEIN OF MYCOBACTERIA IN EARLY CHRONIC ARTHRITIS , 1988, The Lancet.

[28]  C. Janeway,et al.  The immune system evolved to discriminate infectious nonself from noninfectious self. , 1992, Immunology today.

[29]  R. Welsh,et al.  Immunization with a Lymphocytic Choriomeningitis Virus Peptide Mixed with Heat Shock Protein 70 Results in Protective Antiviral Immunity and Specific Cytotoxic T Lymphocytes , 1998, The Journal of experimental medicine.

[30]  D. Mueller T cells: A proliferation of costimulatory molecules , 2000, Current Biology.

[31]  F. Hartl Molecular chaperones in cellular protein folding , 1996, Nature.

[32]  W. Peetermans,et al.  Mycobacterial Heat‐Shock Protein 65 Induces Proinflammatory Cytokines but does not Activate Human Mononuclear Phagocytes , 1994, Scandinavian journal of immunology.

[33]  R. Young,et al.  Heat shock fusion proteins as vehicles for antigen delivery into the major histocompatibility complex class I presentation pathway. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[34]  R. Rappuoli,et al.  Mycobacterial heat‐shock proteins as carrier molecules. II: The use of the 70‐kDa mycobacterial heat‐shock protein as carrier for conjugated vaccinescan circumvent the need for adjuvants and Bacillus Calmette Guérin priming) , 1992, European journal of immunology.

[35]  A. Aderem,et al.  The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens , 1999, Nature.

[36]  J. Winfield,et al.  Brief Definitive Report AUTOANTIBODIES TO THE CONSTITUTIVE 73-kD MEMBER OF THE hsp70 FAMILY OF HEAT SHOCK PROTEINS IN SYSTEMIC LUPUS ERYTHEMATOSUS , 2022 .

[37]  F. Emmrich,et al.  Enumeration of T cells reactive with Mycobacterium tuberculosis organisms and specific for the recombinant mycobacterial 64‐kDa protein , 1987, European journal of immunology.

[38]  M. Miller,et al.  Regulation of murine macrophage IL-12 production. Activation of macrophages in vivo, restimulation in vitro, and modulation by other cytokines. , 1996, Journal of immunology.

[39]  H. Kolb,et al.  Human 60-kDa heat-shock protein: a danger signal to the innate immune system. , 1999, Journal of immunology.

[40]  R. Young,et al.  In Vivo Cytotoxic T Lymphocyte Elicitation by Mycobacterial Heat Shock Protein 70 Fusion Proteins Maps to a Discrete Domain and Is Cd4+ T Cell Independent , 2000, The Journal of experimental medicine.

[41]  H Atlan,et al.  T cell proliferative responses of type 1 diabetes patients and healthy individuals to human hsp60 and its peptides. , 1999, Journal of autoimmunity.

[42]  H. Kolb,et al.  Cutting Edge: Heat Shock Protein 60 Is a Putative Endogenous Ligand of the Toll-Like Receptor-4 Complex1 , 2000, The Journal of Immunology.

[43]  R. van Furth,et al.  Heat shock protein 65 induces CD62e, CD106, and CD54 on cultured human endothelial cells and increases their adhesiveness for monocytes and granulocytes. , 1996, Journal of immunology.

[44]  S. Calderwood,et al.  HSP70 peptide-bearing and peptide-negative preparations act as chaperokines , 2000, Cell stress & chaperones.

[45]  P. Srivastava,et al.  CD91: a receptor for heat shock protein gp96 , 2000, Nature Immunology.

[46]  N. Rosen,et al.  Heat shock protein 90 mediates macrophage activation by Taxol and bacterial lipopolysaccharide. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[47]  P. Srivastava,et al.  Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. , 2000, International immunology.

[48]  Amer A. Beg,et al.  An Essential Role of the NF-κB/Toll-Like Receptor Pathway in Induction of Inflammatory and Tissue-Repair Gene Expression by Necrotic Cells1 , 2001, The Journal of Immunology.

[49]  K. Triantafilou,et al.  A CD14-independent LPS receptor cluster , 2001, Nature Immunology.

[50]  P. Libby,et al.  Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages. , 1999, The Journal of clinical investigation.

[51]  R. Kiessling,et al.  Induction of heat shock protein in monocytic cells by oxidized low density lipoprotein. , 1996, Atherosclerosis.

[52]  P. Srivastava,et al.  Cutting Edge: Heat Shock Protein gp96 Induces Maturation and Migration of CD11c+ Cells In Vivo1 , 2000, The Journal of Immunology.

[53]  T. Wu,et al.  Enhancement of DNA vaccine potency by linkage of antigen gene to an HSP70 gene. , 2000, Cancer research.

[54]  S. Koyasu,et al.  Autoantibodies to the heat-shock protein hsp90 in systemic lupus erythematosus. , 1988, The Journal of clinical investigation.

[55]  J. Cavaillon,et al.  Polymyxin-B inhibition of LPS-induced interleukin-1 secretion by human monocytes is dependent upon the LPS origin. , 1986, Molecular immunology.

[56]  R. Roth,et al.  Hemoglobin: a newly recognized binding protein for bacterial endotoxins (LPS). , 1994, Progress in clinical and biological research.

[57]  R. Issels,et al.  The role of heat shock protein (hsp70) in dendritic cell maturation: Hsp70 induces the maturation of immature dendritic cells but reduces DC differentiation from monocyte precursors , 2001, European journal of immunology.

[58]  J. Salamero,et al.  Heat shock proteins 70 and 60 share common receptors which are expressed on human monocyte‐derived but not epidermal dendritic cells , 2002, European journal of immunology.

[59]  Nina Bhardwaj,et al.  Consequences of cell death: exposure to necrotic tumor cells , 2000 .

[60]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[61]  Carsten J. Kirschning,et al.  Endocytosed HSP60s Use Toll-like Receptor 2 (TLR2) and TLR4 to Activate the Toll/Interleukin-1 Receptor Signaling Pathway in Innate Immune Cells* , 2001, The Journal of Biological Chemistry.

[62]  R. van Furth,et al.  Mycobacterial 65-kilodalton heat shock protein induces tumor necrosis factor alpha and interleukin 6, reactive nitrogen intermediates, and toxoplasmastatic activity in murine peritoneal macrophages , 1995, Infection and immunity.

[63]  D. Remick,et al.  Mycobacterial 65‐kD heat shock protein induces release of proinflammatory cytokines from human monocytic cells , 1993, Clinical and experimental immunology.