Skip to main content
SpringerLink
Log in

HSP Stimulation on Macrophages and Dendritic Cells Activates Innate Immune System

  • Chapter
  • First Online:
Heat Shock Proteins in Inflammatory Diseases

Part of the book series: Heat Shock Proteins ((HESP,volume 22))

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

17-AAG:

17-allylamino-17-demethoxygeldanamycin

APC:

antigen-presenting cell

CRPC:

castration-resistant prostate cancer

CTL:

cytotoxic T lymphocyte

DAMP:

danger-associated molecular pattern

DC:

dendritic cell

ELAM-1:

endothelial cell leukocyte adhesion molecule-1 (also known as E-selectin)

ER:

endoplasmic reticulum

ERK:

extracellular signal-regulated kinase

EV:

extracellular vesicle

HSP:

heat shock proteins

ICAM:

intercellular adhesion molecule

IL:

interleukin

iNOS:

inducible NO synthase

JNK/SAPK:

c-Jun N-terminal kinase

LOX:

low-density lipoprotein receptor

LPS:

lipopolysaccharide (also known as endotoxin)

MAPK:

mitogen-activated protein kinase

MHC:

major histocompatibility complex

MIF:

Macrophage migration inhibitory factor

MMP:

matrix metalloproteinase

MyD88:

myeloid differentiation primary response 88

NBD:

nucleotide-binding domain

NF-κB:

nuclear factor-kappaB

NO:

nitrogen oxide

OSCC:

oral squamous cell carcinoma

SAPK:

stress-activated protein kinase

TAP:

transporter-associated antigen processing

TIR:

toll/IL-1 receptor

TLR:

toll-like receptor

TNF:

tumor necrosis factor

TRAF:

TNF receptor-associated factor

VCAM:

vascular cell adhesion molecule

References

  1. Asea A (2007) Mechanisms of HSP72 release. J Biosci 32(3):579–584. https://doi.org/10.1007/s12038-007-0057-5

    Article  CAS  PubMed  Google Scholar 

  2. Asea A, Kabingu E, Stevenson MA, Calderwood SK (2000a) HSP70 peptide-bearing and peptide-negative preparations act as chaperokines. Cell Stress Chaperones 5(5):425–431. https://doi.org/10.1379/1466-1268(2000)005<0425:HPBAPN>2.0.CO;2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Asea A, Kraeft SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW et al (2000b) HSP70 stimulates cytokine production through a CD 14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6(4):435–442. https://doi.org/10.1038/74697

    Article  CAS  PubMed  Google Scholar 

  4. Asea A, Rehli M, Kabingu E, Boch JA, Baré O, Auron PE et al (2002) Novel signal transduction pathway utilized by extracellular HSP70. Role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem 277(17):15028–15034. https://doi.org/10.1074/jbc.M200497200

    Article  CAS  PubMed  Google Scholar 

  5. Bachelet M, Adrie C, Polla BS (1998) Macrophages and heat shock proteins. Res Immunol 149(7–8):727–732. https://doi.org/10.1016/S0923-2494(99)80047-9

    Article  CAS  PubMed  Google Scholar 

  6. Basu S, Binder RJ, Suto R, Anderson KM, Srivastava PK (2000) Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway. Int Immunol 12(11):1539–1546. https://doi.org/10.1093/intimm/12.11.1539

    Article  CAS  PubMed  Google Scholar 

  7. Basu S, Binder RJ, Ramalingam T, Srivastava PK (2001) CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 14(3):303–313. https://doi.org/10.1016/S1074-7613(01)00111-X

    Article  CAS  PubMed  Google Scholar 

  8. Bendz H, Ruhland SC, Pandya MJ, Hainzl O, Riegelsberger S, Bräuchle C et al (2007) Human heat shock protein 70 enhances tumor antigen presentation through complex formation and intracellular antigen delivery without innate immune signaling. J Biol Chem 282(43):31688–31702. https://doi.org/10.1074/jbc.M704129200

    Article  CAS  PubMed  Google Scholar 

  9. Binder RJ, Han DK, Srivastava PK (2000) CD91: a receptor for heat shock protein gp96. Nat Immunol 1(2):151–155. https://doi.org/10.1038/77835

    Article  CAS  PubMed  Google Scholar 

  10. Blachere NE, Li Z, Chandawarkar RY, Suto R, Jaikaria NS, Basu S et al (1997) Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity. J Exp Med 186(8):1315–1322. https://doi.org/10.1084/jem.186.8.1315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chen W, Syldath U, Bellmann K, Burkart V, Kolb H (1999) Human 60-kDa heat-shock protein: a danger signal to the innate immune system. J Immunol 162(6):3212–3219. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10092772

    CAS  PubMed  Google Scholar 

  12. Eguchi T, Taha E (2020) Extracellular vesicle-associated moonlighting proteins: heat shock proteins and Metalloproteinases. In: Heat shock proteins in human diseases; heat shock proteins, vol 22. Springer Nature

    Google Scholar 

  13. Eguchi T, Calderwood SK, Takigawa M, Kubota S, Kozaki KI (2017) Intracellular MMP3 promotes HSP gene expression in collaboration with Chromobox proteins. J Cell Biochem 118(1):43–51. https://doi.org/10.1002/jcb.25607

    Article  CAS  PubMed  Google Scholar 

  14. Eguchi T, Sogawa C, Okusha Y, Uchibe K, Iinuma R, Ono K et al (2018) Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment. PLoS One 13(e0191109). https://doi.org/10.1371/journal.pone.0191109

  15. Eguchi T, Sogawa C, Ono K, Matsumoto M, Tran MT (2020) Cell stress induced Stressome release including. Cell 9(755)

    Google Scholar 

  16. Gao B, Tsan MF (2003) Recombinant human heat shock protein 60 does not induce the release of tumor necrosis factor α from murine macrophages. J Biol Chem 278(25):22523–22529. https://doi.org/10.1074/jbc.M303161200

    Article  CAS  PubMed  Google Scholar 

  17. Hartl FU (1996) Molecular chaperones in cellular protein folding. Nature 381(6583):571–580. https://doi.org/10.1038/381571a0

    Article  CAS  PubMed  Google Scholar 

  18. Kol A, Sukhova GK, Lichtman AH, Libby P (1998) Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-α and matrix metalloproteinase expression. Circulation 98(4):300–307. https://doi.org/10.1161/01.CIR.98.4.300

    Article  CAS  PubMed  Google Scholar 

  19. Kol A, Bourcier T, Lichtman AH, Libby P (1999) Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages. J Clin Investig 103(4):571–577. https://doi.org/10.1172/JCI5310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kol A, Lichtman AH, Finberg RW, Libby P, Kurt-Jones EA (2000) Cutting edge: heat shock protein (HSP) 60 activates the innate immune response: CD14 is an essential receptor for HSP60 activation of mononuclear cells. J Immunol 164(1):13–17. https://doi.org/10.4049/jimmunol.164.1.13

    Article  CAS  PubMed  Google Scholar 

  21. Kuppner MC, Gastpar R, Gelwer S, Nössner E, Ochmann O, Scharner A, Issels RD (2001) 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. Eur J Immunol 31(5):1602–1609. https://doi.org/10.1002/1521-4141(200105)31:5<1602::AID-IMMU1602>3.0.CO;2-W

    Article  CAS  PubMed  Google Scholar 

  22. Kurotaki T, Tamura Y, Ueda G, Oura J, Kutomi G, Hirohashi Y et al (2007) Efficient cross-presentation by heat shock protein 90-peptide complex-loaded dendritic cells via an endosomal pathway. J Immunol 179(3):1803–1813. https://doi.org/10.4049/jimmunol.179.3.1803

    Article  CAS  PubMed  Google Scholar 

  23. Lehner T, Bergmeier LA, Wang Y, Tao L, Sing M, Spallek R, Van Der Zee R (2000) Heat shock proteins generate β-chemokines which function as innate adjuvants enhancing adaptive immunity. Eur J Immunol 30(2):594–603. https://doi.org/10.1002/1521-4141(200002)30:2<594::AID-IMMU594>3.0.CO;2-1

    Article  CAS  PubMed  Google Scholar 

  24. Liu B, Li S, Xiu B (2019) C-terminus of heat shock protein 60 can activate macrophages by lectin-like oxidized low-density lipoprotein receptor 1. Biochem Biophys Res Commun 508(4):1113–1119. https://doi.org/10.1016/J.BBRC.2018.12.008

    Article  CAS  PubMed  Google Scholar 

  25. Lopez VA, Park BC, Nowak D, Sreelatha A, Zembek P, Fernandez J et al (2019) A bacterial effector mimics a host HSP90 client to undermine immunity. Cell 179(1):205–218.e21. https://doi.org/10.1016/j.cell.2019.08.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. MacMicking J, Xie Q, Nathan C (1997) Nitric oxide and macrophage function. Annu Rev Immunol 15(1):323–350. https://doi.org/10.1146/annurev.immunol.15.1.323

    Article  CAS  PubMed  Google Scholar 

  27. Milani V, Noessner E, Ghose S, Kuppner M, Ahrens B, Scharner A et al (2002) Heat shock protein 70 role in antigen presentation and immune stimulation. Int J Hyperth 6736. https://doi.org/10.1080/0265673021016614

  28. Noessner E, Gastpar R, Milani V, Brandl A, Hutzler PJS, Kuppner MC et al (2002) Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells. J Immunol 169(10):5424–5432. https://doi.org/10.4049/jimmunol.169.10.5424

    Article  CAS  PubMed  Google Scholar 

  29. Okuya K, Tamura Y, Saito K, Kutomi G, Torigoe T, Hirata K, Sato N (2010) Spatiotemporal regulation of heat shock protein 90-chaperoned self-DNA and CpG-Oligodeoxynucleotide for type I IFN induction via targeting to static early endosome. J Immunol 184(12):7092–7099. https://doi.org/10.4049/jimmunol.1000490

    Article  CAS  PubMed  Google Scholar 

  30. Ono K, Eguchi T, Sogawa C (2018) HSP-enriched properties of extracellular vesicles involve survival of metastatic oral cancer cells. J Cell Biochem 119(9):7350–7362. https://doi.org/10.1002/jcb.27039

    Article  CAS  PubMed  Google Scholar 

  31. Ono K, Sogawa C, Kawai H, Tran MT, Taha EA, Lu Y et al (2020) Triple knockdown of CDC37, HSP90-alpha, and HSP90-beta diminishes extracellular vesicles-driven malignancy events and macrophage M2 polarization in oral cancer. J Extracell Vesicles. https://doi.org/10.1080/20013078.2020.1769373

  32. Oura J, Tamura Y, Kamiguchi K, Kutomi G, Sahara H, Torigoe T et al (2011) Extracellular heat shock protein 90 plays a role in translocating chaperoned antigen from endosome to proteasome for generating antigenic peptide to be cross-presented by dendritic cells. Int Immunol 23(4):223–237. https://doi.org/10.1093/intimm/dxq475

    Article  CAS  PubMed  Google Scholar 

  33. Panjwani NN, Popova L, Srivastava PK (2002) Heat shock proteins gp96 and hsp70 activate the release of nitric oxide by APCs. J Immunol 168(6):2997–3003. https://doi.org/10.4049/jimmunol.168.6.2997

    Article  CAS  PubMed  Google Scholar 

  34. Pei W, Tanaka K, Huang SC, Xu L, Liu B, Sinclair J et al (2016) Extracellular HSP60 triggers tissue regeneration and wound healing by regulating inflammation and cell proliferation. Regen Med 1(1):1–11. https://doi.org/10.1038/npjregenmed.2016.13

    Article  Google Scholar 

  35. Randow F, Seed B (2001) Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability. Nat Cell Biol 3(10):891–896. https://doi.org/10.1038/ncb1001-891

    Article  CAS  PubMed  Google Scholar 

  36. Schlesinger MJ (1990) Heat shock proteins. In: Maloy S, Hughes K (eds) Brenner’s encyclopedia of genetics, vol 3, 2nd edn. Elsevier Inc., pp 402–405. https://doi.org/10.1016/B978-0-12-374984-0.00685-9

  37. Schmitt E, Gehrmann M, Brunet M, Multhoff G, Garrido C (2007) Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy. J Leukoc Biol 81(1):15–27. https://doi.org/10.1189/jlb.0306167

    Article  CAS  PubMed  Google Scholar 

  38. Schulz R, Moll UM (2014) Targeting the heat shock protein 90: a rational way to inhibit macrophage migration inhibitory factor function in cancer. Curr Opin Oncol 26(1):108–113. https://doi.org/10.1097/CCO.0000000000000036

    Article  CAS  PubMed  Google Scholar 

  39. Shi Y, Thomas JO (1992) The transport of proteins into the nucleus requires the 70-kilodalton heat shock protein or its cytosolic cognate. Mol Cell Biol 12(5):2186–2192. https://doi.org/10.1128/mcb.12.5.2186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Singh-Jasuja H, Scherer HU, Hilf N, Arnold-Schild D, Rammensee HG, Toes REM, Schild H (2000) The heat shock protein gp96 induces maturation of dendritic cells and down-regulation of its receptor. Eur J Immunol 30(8):2211–2215. https://doi.org/10.1002/1521-4141(2000)30:8<2211::AID-IMMU2211>3.0.CO;2-0

    Article  CAS  PubMed  Google Scholar 

  41. Skeen MJ, Miller MA, Shinnick TM, Ziegler HK (1996) Regulation of murine macrophage IL-12 production. Activation of macrophages in vivo, restimulation in vitro, and modulation by other cytokines. J Immunol 156(3):1196–1206. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8557998

    CAS  PubMed  Google Scholar 

  42. Srivastava P (2002) Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. Annu Rev Immunol 20(1):395–425. https://doi.org/10.1146/annurev.immunol.20.100301.064801

    Article  CAS  PubMed  Google Scholar 

  43. Srivastava PK, Udono H, Blachere NE, Li Z (1994) Heat shock proteins transfer peptides during antigen processing and CTL priming, pp 93–98

    Google Scholar 

  44. Svenssona P-A, Asea A, Englund MCO, Bausero MA et al (2007) Major role of HSP70 as a paracrine inducer of cytokine production in human oxidized LDL treated macrophages. Atherosclerosis 185(1):32–38

    Article  Google Scholar 

  45. Szondy K, Rusai K, Szabó AJ, Nagy A, Gal K, Fekete A et al (2012) Tumor cell expression of heat shock protein (HSP) 72 is influenced by HSP72 [HSPA1B a(1267)G] polymorphism and predicts survival in small cell lung Cancer (SCLC) patients. Cancer Investig 30(4):317–322. https://doi.org/10.3109/07357907.2012.657815

    Article  CAS  Google Scholar 

  46. Taha EA, Ono K, Eguchi T (2019) Roles of extracellular HSPs as biomarkers in immune surveillance and immune evasion. Int J Mol Sci 20(18). https://doi.org/10.3390/ijms20184588

  47. Takeuchi S, Fukuda K, Arai S, Nanjo S, Kita K, Yamada T et al (2016) Organ-specific efficacy of HSP90 inhibitor in multiple-organ metastasis model of chemorefractory small cell lung cancer. Int J Cancer 138(5):1281–1289. https://doi.org/10.1002/ijc.29858

    Article  CAS  PubMed  Google Scholar 

  48. Tamura Y, Peng P, Liu K, Daou M, Srivastava PK (1997) Immunotherapy of Tumors with autologous tumor-derived heat shock protein preparations. Science 278(5335):117 LP–117120. https://doi.org/10.1126/science.278.5335.117

    Article  Google Scholar 

  49. Tanaka T, Okuya K, Kutomi G, Takaya A, Kajiwara T, Kanaseki T et al (2015) Heat shock protein 90 targets a chaperoned peptide to the static early endosome for efficient cross-presentation by human dendritic cells. Cancer Sci 106(1):18–24. https://doi.org/10.1111/cas.12570

    Article  CAS  PubMed  Google Scholar 

  50. Tsan MF, Gao B (2004) Heat shock protein and innate immunity. Cell Mol Immunol 1(4):274–279. https://doi.org/10.0000/014198799329495

    Article  CAS  PubMed  Google Scholar 

  51. Ueda G, Tamura Y, Hirai I, Kamiguchi K, Ichimiya S, Torigoe T et al (2004) Tumor-derived heat shock protein 70-pulsed dendritic cells elicit-tumor-specific cytotoxic T lymphocytes (CTLs) and tumor immunity. Cancer Sci 95(3):248–253. https://doi.org/10.1111/j.1349-7006.2004.tb02211.x

    Article  CAS  PubMed  Google Scholar 

  52. Vabulas RM, Ahmad-Nejad P, Da Costa C, Miethke T, Kirschning CJ, Häcker H, Wagner H (2001) Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/Interleukin-1 receptor Signaling pathway in innate immune cells. J Biol Chem 276(33):31332–31339. https://doi.org/10.1074/jbc.M103217200

    Article  CAS  PubMed  Google Scholar 

  53. Vabulas RM, Ahmad-Nejad P, Ghose S, Kirschning CJ, Issels RD, Wagner H (2002) HSP70 as endogenous stimulus of the toll/interleukin-1 receptor signal pathway. J Biol Chem 277(17):15107–15112. https://doi.org/10.1074/jbc.M111204200

    Article  CAS  PubMed  Google Scholar 

  54. Wallin RPA, Lundqvist A, Moré SH, Von Bonin A, Kiessling R, Ljunggren HG (2002) Heat-shock proteins as activators of the innate immune system. Trends Immunol 23(3):130–135. https://doi.org/10.1016/S1471-4906(01)02168-8

    Article  CAS  PubMed  Google Scholar 

  55. Yang Y, Liu B, Dai J, Srivastava PK, Zammit DJ, Lefrançois L, Li Z (2007) Heat shock protein gp96 is a master chaperone for toll-like receptors and is important in the innate function of macrophages. Immunity 26(2):215–226. https://doi.org/10.1016/j.immuni.2006.12.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zheng L, He M, Long M, Blomgran R, Stendahl O (2004) Pathogen-induced apoptotic neutrophils express heat shock proteins and elicit activation of human macrophages. J Immunol 173(10):6319–6326. https://doi.org/10.4049/jimmunol.173.10.6319

    Article  CAS  PubMed  Google Scholar 

  57. Zhou F, Xing D, Chen WR (2009) Regulation of HSP70 on activating macrophages using PDT-induced apoptotic cells. Int J Cancer 125(6):1380–1389. https://doi.org/10.1002/ijc.24520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors thank Takuya Miyawaki, Chiharu Sogawa, Kuniaki Okamoto, Yuka Okusha, Eman A. Taha for their cooperation, mentorship, or support. T.E. was supported by JSPS KAKENHI, grant numbers, JP17K11642-TE, JP17K11669-KOh, JP18K09789-KN, 19H04051-HO, 19H03817-MT, and by Suzuki Kenzo Memorial Foundation. Y.L. was supported by Rotary Yoneyama Memorial Foundation.

Disclosure of Interests

The authors declare no conflict of interest with the content of this study.

Ethical Approval for Studies Involving Humans

This article does not contain any studies with human participants performed by any of the authors.

Ethical Approval for Studies Involving Animals

This article does not contain any studies with animals performed by any of the authors.

Author information

Author notes

  1. Yanyin Lu and Takanori Eguchi contributed equally with all other contributors.

Authors and Affiliations

  1. Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan

    Yanyin Lu & Takanori Eguchi

  2. Department of Dental Anesthesiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan

    Yanyin Lu

Authors
  1. Yanyin Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takanori Eguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takanori Eguchi .

Editor information

Editors and Affiliations

  1. Department of Medicine and Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

    Alexzander A. A. Asea

  2. Department of Medicine and Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

    Punit Kaur

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lu, Y., Eguchi, T. (2020). HSP Stimulation on Macrophages and Dendritic Cells Activates Innate Immune System. In: Asea, A.A.A., Kaur, P. (eds) Heat Shock Proteins in Inflammatory Diseases. Heat Shock Proteins, vol 22. Springer, Cham. https://doi.org/10.1007/7515_2020_26

Download citation

Publish with us

Policies and ethics

Search

Navigation