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2000
Volume 2, Issue 2
  • ISSN: 2666-1217
  • E-ISSN: 2666-1225

Abstract

Snake envenomations are one of the most common venomous accidents caused by snakes in the world. The symptoms induced after bite vary accordingly to the species. Most of the snake venoms elicit direct or indirect activation of the innate immune responses that ranges from local to systemic effects and contributes to the clinical manifestations after envenoming. The venom interacts with the immune system by inducing the release of damage-associated molecular patterns, which contributes to create a proinflamatory status, release of cytokines and lipid mediators, and has properties to modulate other components of the innate immune system like the complement system. In this review, we highlight some studies that point out over the years the mechanisms by which snake venoms interact with the innate immune system, as well as the pharmacological potential of this class of compounds with great applicability to the medical field.

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2025-11-05

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References

  1. NicholsonL.B. The immune system.Essays Biochem.201660327530110.1042/EBC20160017 27784777
     [Google Scholar]
  2. MedzhitovR. Recognition of microorganisms and activation of the immune response.Nature2007449716481982610.1038/nature06246 17943118
     [Google Scholar]
  3. ChaplinD.D. Overview of the immune response.J. Allergy Clin. Immunol.20101252Suppl. 2S3S2310.1016/j.jaci.2009.12.980 20176265
     [Google Scholar]
  4. KumarH. KawaiT. AkiraS. Pathogen recognition by the innate immune system.Int. Rev. Immunol.2011301163410.3109/08830185.2010.529976 21235323
     [Google Scholar]
  5. ZoccalKF SorgiCA HoriJI Opposing roles of LTB4 and PGE2 in regulating the inflammasome-dependent scorpion venominduced mortality TL - 7. Nat Commun20167VN-re: 10760
     [Google Scholar]
  6. ReisM.B. ZoccalK.F. GardinassiL.G. FaccioliL.H. Scorpion envenomation and inflammation: Beyond neurotoxic effects.Toxicon201916717417910.1016/j.toxicon.2019.06.219 31228480
     [Google Scholar]
  7. ReisM.B. RodriguesF.L. LautherbachN. Interleukin-1 receptor-induced PGE2 production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation.Nat. Commun.2020111543310.1038/s41467‑020‑19232‑8 33116136
     [Google Scholar]
  8. PalmN.W. MedzhitovR. Role of the inflammasome in defense against venoms.Proc. Natl. Acad. Sci. USA201311051809181410.1073/pnas.1221476110 23297192
     [Google Scholar]
  9. FerreiraM.J. LimaC. Lopes-FerreiraM. Anti-inflammatory effect of Natterins, the major toxins from the Thalassophryne nattereri fish venom is dependent on TLR4/MyD88/PI3K signaling pathway.Toxicon201487546710.1016/j.toxicon.2014.05.014 24882373
     [Google Scholar]
  10. PatelK.D. ModurV. ZimmermanG.A. PrescottS.M. McIntyreT.M. The necrotic venom of the brown recluse spider induces dysregulated endothelial cell-dependent neutrophil activation. Differential induction of GM-CSF, IL-8, and E-selectin expression.J. Clin. Invest.199494263164210.1172/JCI117379 7518841
     [Google Scholar]
  11. LeónG. SánchezL. HernándezA. Immune response towards snake venoms.Inflamm. Allergy Drug Targets201110538139810.2174/187152811797200605 21824081
     [Google Scholar]
  12. BernardesC.P. MenaldoD.L. MamedeC.C.N. Evaluation of the local inflammatory events induced by BpirMP, a metalloproteinase from Bothrops pirajai venom.Mol. Immunol.2015682 Pt B45646410.1016/j.molimm.2015.09.023 26468034
     [Google Scholar]
  13. MetzM PiliponskyAM ChanCC Mast cells can enhance resistance to snake and honeybee venoms.Science (80- )200631352630
     [Google Scholar]
  14. CostaT.R. MenaldoD.L. ZoccalK.F. CR-LAAO, an L-amino acid oxidase from Calloselasma rhodostoma venom, as a potential tool for developing novel immunotherapeutic strategies against cancer.Sci. Rep.2017714267310.1038/srep42673 28205610
     [Google Scholar]
  15. CalveteJ.J. JuárezP. SanzL. Snake venomics. Strategy and applications.J. Mass Spectrom.200742111405141410.1002/jms.1242 17621391
     [Google Scholar]
  16. MoreiraV. TeixeiraC. Borges da SilvaH. D’Império LimaM.R. Dos-SantosM.C. The role of TLR2 in the acute inflammatory response induced by Bothrops atrox snake venom.Toxicon201611812112810.1016/j.toxicon.2016.04.042 27109323
     [Google Scholar]
  17. GutiérrezJ.M. OwnbyC.L. OdellG.V. Pathogenesis of myonecrosis induced by crude venom and a myotoxin of Bothrops asper.Exp. Mol. Pathol.198440336737910.1016/0014‑4800(84)90054‑6 6539250
     [Google Scholar]
  18. HsuC.C. ChuangW.J. ChungC.H. ChangC.H. PengH.C. HuangT.F. Snake venom disintegrin inhibits the activation of toll-like receptors and alleviates sepsis through integrin alphavbeta3 blockade.Sci. Rep.2016612338710.1038/srep23387 26987407
     [Google Scholar]
  19. ZoccalK.F. BitencourtC.S. Paula-SilvaF.W.G. TLR2, TLR4 and CD14 recognize venom-associated molecular patterns from Tityus serrulatus to induce macrophage-derived inflammatory mediators.PLoS One201492e8817410.1371/journal.pone.0088174 24516606
     [Google Scholar]
  20. TeixeiraC. FernandesC.M. LeiguezE. Chudzinski-TavassiA.M. Inflammation induced by platelet-activating viperid snake venoms: Perspectives on thromboinflammation.Front. Immunol.201910208210.3389/fimmu.2019.02082 31572356
     [Google Scholar]
  21. Paiva-OliveiraE.L. da SilvaR.F. BellioM. Quirico-SantosT. Lagrota-CandidoJ. Pattern of cardiotoxin-induced muscle remodeling in distinct TLR-4 deficient mouse strains.Histochem. Cell Biol.20171481496010.1007/s00418‑017‑1556‑6 28293722
     [Google Scholar]
  22. MoreiraV. TeixeiraC. Borges da SilvaH. D’Império LimaM.R. Dos-SantosM.C. The crucial role of the MyD88 adaptor protein in the inflammatory response induced by Bothrops atrox venom.Toxicon201367374610.1016/j.toxicon.2013.02.010 23474268
     [Google Scholar]
  23. CezaretteG.N. SartimM.A. SampaioS.V. Inflammation and coagulation crosstalk induced by BJcuL, a galactose-binding lectin isolated from Bothrops jararacussu snake venom.Int. J. Biol. Macromol.202014429630410.1016/j.ijbiomac.2019.12.015 31812742
     [Google Scholar]
  24. TadokoroT. ModahlM.C. MaenakaK. Aoki-ShioiN. Cysteine-rich secretory proteins (CRISPs) from venomous snakes: An overview of the functional diversity in a large and underappreciated superfamily.Toxins (Basel)20201217510.3390/toxins12030175
     [Google Scholar]
  25. DekaA. SharmaM. MukhopadhyayR. DeviA. DoleyR. Naja kaouthia venom protein, Nk-CRISP, upregulates inflammatory gene expression in human macrophages.Int. J. Biol. Macromol.202016060261110.1016/j.ijbiomac.2020.05.169 32470580
     [Google Scholar]
  26. KuoY.J. ChungC.H. HuangT.F. From discovery of snake venom disintegrins to a safer therapeutic antithrombotic agent.Toxins (Basel)20191171110.3390/toxins12010011 31247995
     [Google Scholar]
  27. LeiguezE. GiannottiK.C. MoreiraV. Critical role of TLR2 and MyD88 for functional response of macrophages to a group IIA-secreted phospholipase A2 from snake venom.PLoS One201494e9374110.1371/journal.pone.0093741 24718259
     [Google Scholar]
  28. RucavadoA. NicolauC.A. EscalanteT. Viperid envenomation wound exudate contributes to increased vascular permeability via a DAMPs/TLR-4 mediated pathway.Toxins (Basel)201681234910.3390/toxins8120349 27886127
     [Google Scholar]
  29. LunaK.P.O. da SilvaM.B. PereiraV.R.A. Clinical and immunological aspects of envenomations by Bothrops snakes.J. Venom. Anim. Toxins Incl. Trop. Dis.201117213014110.1590/S1678‑91992011000200003
     [Google Scholar]
  30. GonçalvesA.S. AppelbergR. Modulation of neutrophil influx with cell adhesion molecule specific antibodies during nonspecific and immune mediated inflammatory reactions.Scand. J. Immunol.200051548549010.1046/j.1365‑3083.2000.00720.x 10792840
     [Google Scholar]
  31. MiddletonJ. PattersonA.M. GardnerL. SchmutzC. AshtonB.A. Leukocyte extravasation: Chemokine transport and presentation by the endothelium.Blood2002100123853386010.1182/blood.V100.12.3853 12433694
     [Google Scholar]
  32. KamiuchiK. HasegawaG. ObayashiH. Leukocyte-endothelial cell adhesion molecule 1 (LECAM-1) polymorphism is associated with diabetic nephropathy in type 2 diabetes mellitus.J. Diabetes Complications200216533333710.1016/S1056‑8727(01)00226‑4 12200076
     [Google Scholar]
  33. RyanG.B. MajnoG. Acute inflammation. A review.Am. J. Pathol.1977861183276 64118
     [Google Scholar]
  34. Witko-SarsatV. RieuP. Descamps-LatschaB. LesavreP. Halbwachs-MecarelliL. Neutrophils: molecules, functions and pathophysiological aspects.Lab. Invest.200080561765310.1038/labinvest.3780067 10830774
     [Google Scholar]
  35. ZamunerS.R. ZulianiJ.P. FernandesC.M. GutiérrezJ.M. de Fátima Pereira TeixeiraC. Inflammation induced by Bothrops asper venom: release of proinflammatory cytokines and eicosanoids, and role of adhesion molecules in leukocyte infiltration.Toxicon200546780681310.1016/j.toxicon.2005.08.011 16198389
     [Google Scholar]
  36. SteeberD.A. TangM.L.K. GreenN.E. ZhangX.Q. SloaneJ.E. TedderT.F. Leukocyte entry into sites of inflammation requires overlapping interactions between the L-selectin and ICAM-1 pathways.J. Immunol.1999163421762186 10438959
     [Google Scholar]
  37. FernandesC.M. ZamunerS.R. ZulianiJ.P. RucavadoA. GutiérrezJ.M. TeixeiraC.F. Inflammatory effects of BaP1 a metalloproteinase isolated from Bothrops asper snake venom: leukocyte recruitment and release of cytokines.Toxicon200647554955910.1016/j.toxicon.2006.01.009 16529786
     [Google Scholar]
  38. WalcheckB. AlexanderS.R. St HillC.A. MatalaE. ADAM-17-independent shedding of L-selectin.J. Leukoc. Biol.200374338939410.1189/jlb.0403141 12949242
     [Google Scholar]
  39. WangY.L. KuoJ.H. LeeS.C. Cobra CRISP functions as an inflammatory modulator via a novel Zn2+- and heparan sulfate-dependent transcriptional regulation of endothelial cell adhesion molecules.J. Biol. Chem.201028548378723788310.1074/jbc.M110.146290 20889969
     [Google Scholar]
  40. FloresC.A. ZappelliniA. Prado-FranceschiJ. Lipoxygenase-derived mediators may be involved in in vivo neutrophil migration induced by Bothrops erythromelas and Bothrops alternatus venoms.Toxicon199331121551155910.1016/0041‑0101(93)90339‑K 8146868
     [Google Scholar]
  41. SartimM.A. RiulT.B. Del Cistia-AndradeC. Galatrox is a C-type lectin in Bothrops atrox snake venom that selectively binds LacNAc-terminated glycans and can induce acute inflammation.Glycobiology201424111010102110.1093/glycob/cwu061 24973254
     [Google Scholar]
  42. ArendW.P. GabayC. Cytokines in the rheumatic diseases.Rheum. Dis. Clin. North Am.20043014167[v-vi.]10.1016/S0889‑857X(03)00115‑715061568
     [Google Scholar]
  43. AkiraS. HiranoT. TagaT. KishimotoT. Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF).FASEB J.19904112860286710.1096/fasebj.4.11.2199284 2199284
     [Google Scholar]
  44. MedeirosA.I. SilvaC.L. MalheiroA. MaffeiC.M.L. FaccioliL.H. Leukotrienes are involved in leukocyte recruitment induced by live Histoplasma capsulatum or by the β-glucan present in their cell wall.Br. J. Pharmacol.199912871529153710.1038/sj.bjp.0702912 10602333
     [Google Scholar]
  45. FlamandN. MancusoP. SerezaniC.H.C. BrockT.G. Leukotrienes: mediators that have been typecast as villains.Cell. Mol. Life Sci.20076419-202657267010.1007/s00018‑007‑7228‑2 17639273
     [Google Scholar]
  46. SetúbalS.D.S. PontesA.S. NeryN.M. Human neutrophils functionality under effect of an Asp49 phospholipase A2 isolated from Bothrops atrox venom.Toxicon X2020610003210.1016/j.toxcx.2020.100032 32550587
     [Google Scholar]
  47. RuipérezV. AstudilloA.M. BalboaM.A. BalsindeJ. Coordinate regulation of TLR-mediated arachidonic acid mobilization in macrophages by group IVA and group V phospholipase A2s.J. Immunol.200918263877388310.4049/jimmunol.0804003 19265167
     [Google Scholar]
  48. ZambelliV.O. SampaioS.C. Sudo-HayashiL.S. Crotoxin alters lymphocyte distribution in rats: Involvement of adhesion molecules and lipoxygenase-derived mediators.Toxicon20085181357136710.1016/j.toxicon.2008.03.004 18452962
     [Google Scholar]
  49. SampaioS.C. Rangel-SantosA.C. PeresC.M. CuriR. CuryY. Inhibitory effect of phospholipase A2 isolated from Crotalus durissus terrificus venom on macrophage function.Toxicon200545567167610.1016/j.toxicon.2005.01.009 15777963
     [Google Scholar]
  50. WiedleG. DunonD. ImhofB.A. Current concepts in lymphocyte homing and recirculation.Crit. Rev. Clin. Lab. Sci.200138113110.1080/20014091084164 11256516
     [Google Scholar]
  51. FunkCD Prostaglandins and leukotrienes: Advances in eicosanoid biology.Science (80- )200129418715
     [Google Scholar]
  52. KiniR.M. Excitement ahead: structure, function and mechanism of snake venom phospholipase A2 enzymes.Toxicon200342882784010.1016/j.toxicon.2003.11.002 15019485
     [Google Scholar]
  53. VianaM.N. LeiguezE. GutiérrezJ.M. A representative metalloprotease induces PGE2 synthesis in fibroblast-like synoviocytes via the NF-κB/COX-2 pathway with amplification by IL-1β and the EP4 receptor.Sci. Rep.202010111510.1038/s41598‑020‑59095‑z
     [Google Scholar]
  54. TeixeiraC.F. FernandesC.M. ZulianiJ.P. ZamunerS.F. Inflammatory effects of snake venom metalloproteinases.Mem. Inst. Oswaldo Cruz2005100Suppl. 118118410.1590/S0074‑02762005000900031 15962120
     [Google Scholar]
  55. StoneS.F. IsbisterG.K. ShahmyS. Immune response to snake envenoming and treatment with antivenom; complement activation, cytokine production and mast cell degranulation.PLoS Negl. Trop. Dis.201377e232610.1371/journal.pntd.0002326 23936562
     [Google Scholar]
  56. KatkarG.D. SundaramM.S. HemshekharM. Melatonin alleviates Echis carinatus venom-induced toxicities by modulating inflammatory mediators and oxidative stress.J. Pineal Res.201456329531210.1111/jpi.12123 24499241
     [Google Scholar]
  57. De CarvalhoAEZ GiannottiK JuniorEL Crotalus durissus ruruima snake venom and a phospholipase A2 isolated from this venom elicit macrophages to form lipid droplets and synthesize inflammatory lipid mediators.J Immunol Res20192019
     [Google Scholar]
  58. MitrmoonpitakC. ChulasugandhaP. KhowO. NoipromJ. ChaiyabutrN. SitprijaV. Effects of phospholipase A2 and metalloprotease fractions of Russell’s viper venom on cytokines and renal hemodynamics in dogs.Toxicon201361475310.1016/j.toxicon.2012.10.017 23142505
     [Google Scholar]
  59. CarrollM.C. The complement system in regulation of adaptive immunity.Nat. Immunol.200451098198610.1038/ni1113 15454921
     [Google Scholar]
  60. Pidde-QueirozG. FurtadoM de F. FilgueirasC.F. Human complement activation and anaphylatoxins generation induced by snake venom toxins from Bothrops genus.Mol. Immunol.201047162537254410.1016/j.molimm.2010.07.003 20674029
     [Google Scholar]
  61. WalportM.J. Complement. First of two parts.N. Engl. J. Med.2001344141058106610.1056/NEJM200104053441406 11287977
     [Google Scholar]
  62. TurnerM.W. Mannose-binding lectin: The pluripotent molecule of the innate immune system.Immunol. Today1996171153254010.1016/S0167‑5699(96)80908‑X 8961631
     [Google Scholar]
  63. FarskyS.H.P. GonçalvesL.R.C. GutiérrezJ.M. Bothrops asper snake venom and its metalloproteinase BaP-1 activate the complement system. Role in leucocyte recruitment.Mediators Inflamm.20009521322110.1080/09629350020025728 11200361
     [Google Scholar]
  64. MenaldoD.L. BernardesC.P. PereiraJ.C. Effects of two serine proteases from Bothrops pirajai snake venom on the complement system and the inflammatory response.Int. Immunopharmacol.201315476477110.1016/j.intimp.2013.02.023 23499645
     [Google Scholar]
  65. VogelC.W. FritzingerD.C. Cobra venom factor: Structure, function, and humanization for therapeutic complement depletion.Toxicon20105671198122210.1016/j.toxicon.2010.04.007 20417224
     [Google Scholar]
  66. Pidde-QueirozG. MagnoliF.C. PortaroF.C.V. P-I snake venom metalloproteinase is able to activate the complement system by direct cleavage of central components of the cascade.PLoS Negl. Trop. Dis.2013710e251910.1371/journal.pntd.0002519 24205428
     [Google Scholar]
  67. TanakaG.D. Pidde-QueirozG. de FátimaD. FurtadoM. van den BergC. TambourgiD.V. Micrurus snake venoms activate human complement system and generate anaphylatoxins.BMC Immunol.2012131410.1186/1471‑2172‑13‑4 22248157
     [Google Scholar]
  68. GötzeO. Müller-EberhardH.J. The c3-activator system: An alternate pathway of complement activation.J. Exp. Med.197113439010810.1084/jem.134.3.90 19867385
     [Google Scholar]
  69. VogelC.W. Müller-EberhardH.J. The cobra venom factordependent C3 convertase of human complement. A kinetic and thermodynamic analysis of a protease acting on its natural high molecular weight substrate - PubMedAvailable from: https://pubmed.ncbi.nlm.nih.gov/6919543/ (accessed on Apr 29, 2021).
  70. AyresL.R. RécioA dos R. BurinS.M. Bothrops snake venoms and their isolated toxins, an L-amino acid oxidase and a serine protease, modulate human complement system pathways.J. Venom. Anim. Toxins Incl. Trop. Dis.20152112910.1186/s40409‑015‑0026‑7 26273289
     [Google Scholar]
  71. MenaldoDL Jacob-FerreiraAL BernardesCP CintraACO SampaioSV Purification procedure for the isolation of a P-I metalloprotease and an acidic phospholipase A2 from Bothrops atrox snake venom.J Venom Anim Toxins Incl Trop Dis2015210-010.1186/s40409‑015‑0027‑6
     [Google Scholar]
  72. MenaldoD.L. BernardesC.P. Jacob-FerreiraA.L. Effects of Bothrops atrox venom and two isolated toxins on the human complement system: Modulation of pathways and generation of anaphylatoxins.Mol. Immunol.2016809110010.1016/j.molimm.2016.10.015 27846429
     [Google Scholar]
  73. OlaobaO.T. Karina Dos SantosP. Selistre-de-AraujoH.S. Ferreira de SouzaD.H. Snake venom metalloproteinases (SVMPs): A structure-function update.Toxicon X2020710005210.1016/j.toxcx.2020.100052 32776002
     [Google Scholar]
  74. SampaioS.C. HyslopS. FontesM.R.M. Crotoxin: Novel activities for a classic β-neurotoxin.Toxicon20105561045106010.1016/j.toxicon.2010.01.011 20109480
     [Google Scholar]
  75. QueirozG.P. PessoaL.A. PortaroF.C.V. FurtadoM de FD. TambourgiD.V. Interspecific variation in venom composition and toxicity of Brazilian snakes from Bothrops genus.Toxicon200852884285110.1016/j.toxicon.2008.10.002 18983867
     [Google Scholar]
  76. DelafontaineM Villas-BoasIM PiddeG Venom from bothrops lanceolatus, a snake species native to Martinique, potently activates the complement system.J Immunol Res20182018
     [Google Scholar]
  77. SzoldO. Ben-AbrahamR. WeinbroumA.A. Antagonization of TNF attenuates systemic hemodynamic manifestations of envenomation in a rat model of Vipera aspis snakebite.Intensive Care Med.200127588488810.1007/s001340100875 11430545
     [Google Scholar]
  78. SzoldO. Ben-AbrahamR. FrolkisI. SorkineM. SorkineP. Tumor necrosis factor as a mediator of cardiac toxicity following snake envenomation.Crit. Care Med.20033151449145310.1097/01.CCM.0000050440.87890.92 12771617
     [Google Scholar]
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Snake Envenomation and Innate Immune System: An Overview
Ven and Tox 2, e230522205123 (2022); https://doi.org/10.2174/2666121702666220523140901
/content/journals/vat/10.2174/2666121702666220523140901
/content/journals/vat/10.2174/2666121702666220523140901
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  • Article Type:     Review Article
Keyword(s): complement system; cytokines; inflammation; neutrophils; Snake venom; toll-like receptors

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