Cathelicidin Host Defense Peptides and Inflammatory Signaling: Striking a Balance.

Morgan A Alford, Beverlie Baquir, Felix L Santana, Evan F Haney, Robert E W Hancock
Author Information
  1. Morgan A Alford: Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
  2. Beverlie Baquir: Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
  3. Felix L Santana: Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
  4. Evan F Haney: Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
  5. Robert E W Hancock: Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.

Abstract

Host-defense peptides (HDPs) are vital components of innate immunity in all vertebrates. While their antibacterial activity toward bacterial cells was the original focus for research, their ability to modulate immune and inflammatory processes has emerged as one of their major functions in the host and as a promising approach from which to develop novel therapeutics targeting inflammation and innate immunity. In this review, with particular emphasis on the cathelicidin family of peptides, the roles of natural HDPs are examined in managing immune activation, cellular recruitment, cytokine responses, and inflammation in response to infection, as well as their contribution(s) to various inflammatory disorders and autoimmune diseases. Furthermore, we discuss current efforts to develop synthetic HDPs as therapeutics aimed at restoring balance to immune responses that are dysregulated and contribute to disease pathologies.

Keywords

References

  1. Ann N Y Acad Sci. 2014 Sep;1323:101-14 [PMID: 24797961]
  2. Vaccine. 2008 Mar 20;26(13):1626-37 [PMID: 18295941]
  3. Am J Respir Cell Mol Biol. 2010 Dec;43(6):692-702 [PMID: 20097832]
  4. J Biol Chem. 2014 Oct 3;289(40):27614-24 [PMID: 25092290]
  5. Front Pharmacol. 2019 Nov 29;10:1415 [PMID: 31849667]
  6. Zool Res. 2019 Mar 18;40(2):94-101 [PMID: 30127328]
  7. J Invest Dermatol. 2003 Mar;120(3):379-89 [PMID: 12603850]
  8. Blood. 2009 Feb 12;113(7):1399-407 [PMID: 18757776]
  9. Semin Cell Dev Biol. 2019 Apr;88:163-172 [PMID: 29501617]
  10. Int J Antimicrob Agents. 2009 Nov;34(5):457-61 [PMID: 19524411]
  11. Nanomedicine. 2019 Aug;20:102022 [PMID: 31170510]
  12. PLoS One. 2013;8(1):e52449 [PMID: 23308112]
  13. Science. 2020 May 1;368(6490): [PMID: 32355003]
  14. Rheumatology (Oxford). 2017 Nov 1;56(11):1945-1961 [PMID: 28968809]
  15. Hum Reprod. 2002 Oct;17(10):2529-34 [PMID: 12351523]
  16. Drug Deliv. 2016 May;23(4):1163-70 [PMID: 25693639]
  17. ACS Omega. 2020 Apr 14;5(16):9301-9310 [PMID: 32363280]
  18. Trends Mol Med. 2014 Apr;20(4):195-203 [PMID: 24581450]
  19. Mol Cell Proteomics. 2014 Feb;13(2):397-406 [PMID: 24309898]
  20. Vaccine. 2013 Jun 28;31(31):3148-55 [PMID: 23684829]
  21. RSC Adv. 2018 Aug 6;8(49):28013-28023 [PMID: 35542741]
  22. ACS Infect Dis. 2019 Mar 8;5(3):443-453 [PMID: 30565465]
  23. Immunology. 2002 May;106(1):20-6 [PMID: 11972628]
  24. J Immunol. 2002 Oct 1;169(7):3883-91 [PMID: 12244186]
  25. Acta Vet Scand. 2017 May 19;59(1):31 [PMID: 28526080]
  26. Infect Immun. 2012 Dec;80(12):4485-94 [PMID: 23045480]
  27. J Immunol. 2014 Jun 1;192(11):5363-72 [PMID: 24771854]
  28. Cell Physiol Biochem. 2018;47(3):1060-1073 [PMID: 29843147]
  29. J Immunol Res. 2018 Feb 19;2018:7357162 [PMID: 29670923]
  30. Future Microbiol. 2011 Jun;6(6):635-51 [PMID: 21707311]
  31. Biochem J. 2017 Aug 10;474(16):2861-2885 [PMID: 28798159]
  32. Nat Med. 2007 Aug;13(8):975-80 [PMID: 17676051]
  33. Front Biosci. 2008 May 01;13:3760-7 [PMID: 18508470]
  34. PLoS One. 2015 Sep 22;10(9):e0138340 [PMID: 26394045]
  35. J Immunol. 2004 Mar 1;172(5):3070-7 [PMID: 14978112]
  36. Peptides. 2003 Nov;24(11):1655-67 [PMID: 15019197]
  37. J Intern Med. 2003 Sep;254(3):197-215 [PMID: 12930229]
  38. Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1551-7 [PMID: 16645154]
  39. Pediatr Infect Dis J. 2018 Feb;37(2):182-185 [PMID: 28827496]
  40. Nat Commun. 2020 Jan 8;11(1):105 [PMID: 31913271]
  41. J Biol Chem. 2006 Feb 3;281(5):2858-67 [PMID: 16326712]
  42. J Invest Dermatol. 2013 Feb;133(2):377-85 [PMID: 23014338]
  43. J Innate Immun. 2010;2(5):478-82 [PMID: 20571257]
  44. Nat Rev Immunol. 2017 Jul;17(7):407-420 [PMID: 28436424]
  45. Immune Netw. 2020 Feb 04;20(2):e15 [PMID: 32395367]
  46. Wound Repair Regen. 2014 Sep-Oct;22(5):613-21 [PMID: 25041740]
  47. J Immunol. 2013 Nov 15;191(10):4895-901 [PMID: 24185823]
  48. Br J Surg. 2001 Jan;88(1):22-30 [PMID: 11136305]
  49. Curr Issues Mol Biol. 2005 Jul;7(2):179-96 [PMID: 16053249]
  50. Peptides. 2016 Nov;85:16-26 [PMID: 27609777]
  51. Front Immunol. 2019 Jul 26;10:1764 [PMID: 31402919]
  52. Front Chem. 2019 Feb 04;7:43 [PMID: 30778385]
  53. J Dermatol Sci. 2012 Jan;65(1):19-26 [PMID: 22047630]
  54. Dev Comp Immunol. 2019 Sep;98:189-204 [PMID: 31121185]
  55. Nat Chem Biol. 2013 Dec;9(12):761-8 [PMID: 24231617]
  56. Nat Rev Nephrol. 2018 Feb;14(2):121-137 [PMID: 29225343]
  57. Mol Immunol. 2008 Jan;45(1):204-17 [PMID: 17709140]
  58. Vasc Med. 2015 Apr;20(2):168-81 [PMID: 25832604]
  59. Int Immunol. 2006 Dec;18(12):1729-36 [PMID: 17041145]
  60. Infect Immun. 2000 May;68(5):2748-55 [PMID: 10768969]
  61. Biol Rev Camb Philos Soc. 1997 Aug;72(3):365-79 [PMID: 9336100]
  62. Sci Transl Med. 2011 Mar 9;3(73):73ra19 [PMID: 21389263]
  63. J Innate Immun. 2014;6(2):205-18 [PMID: 23969854]
  64. Crit Care Med. 2013 Mar;41(3):706-16 [PMID: 23425819]
  65. Antimicrob Agents Chemother. 2006 May;50(5):1672-9 [PMID: 16641434]
  66. Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4498-508 [PMID: 17898271]
  67. Chem Biol Drug Des. 2019 Jun;93(6):1175-1185 [PMID: 30635992]
  68. Int J Antimicrob Agents. 2012 Jan;39(1):39-44 [PMID: 22005071]
  69. Probiotics Antimicrob Proteins. 2020 Mar;12(1):64-72 [PMID: 31686299]
  70. Infect Immun. 1996 Dec;64(12):4922-7 [PMID: 8945527]
  71. J Immunol. 2011 Jun 15;186(12):7243-54 [PMID: 21576504]
  72. BMC Pulm Med. 2013 Apr 16;13:23 [PMID: 23590701]
  73. Nat Rev Immunol. 2008 Oct;8(10):776-87 [PMID: 18802444]
  74. J Immunol. 2004 Jan 15;172(2):1146-56 [PMID: 14707090]
  75. Pharmaceuticals (Basel). 2014 Mar 03;7(3):265-310 [PMID: 24594555]
  76. J Cell Biochem. 2019 Apr;120(4):4863-4871 [PMID: 30537236]
  77. Microbes Infect. 2002 Mar;4(3):361-72 [PMID: 11909747]
  78. Int Immunopharmacol. 2017 Aug;49:6-12 [PMID: 28549244]
  79. J Innate Immun. 2012;4(4):377-86 [PMID: 22516952]
  80. Semin Immunopathol. 2017 Jul;39(5):517-528 [PMID: 28555385]
  81. J Immunol. 2004 Sep 1;173(5):2909-12 [PMID: 15322146]
  82. J Exp Med. 2000 Oct 2;192(7):1069-74 [PMID: 11015447]
  83. Arch Immunol Ther Exp (Warsz). 2017 Oct;65(5):455-461 [PMID: 27663530]
  84. Theranostics. 2019 Apr 12;9(8):2209-2223 [PMID: 31149039]
  85. Lancet. 2019 Feb 2;393(10170):423-433 [PMID: 30635141]
  86. Int Immunopharmacol. 2018 Dec;65:382-391 [PMID: 30380513]
  87. Clin Infect Dis. 2017 Sep 15;65(6):967-975 [PMID: 28541502]
  88. Genetics. 2007 Nov;177(3):1941-9 [PMID: 17947411]
  89. FASEB J. 2005 Jul;19(9):1067-77 [PMID: 15985530]
  90. Am J Perinatol. 2014 Dec;31(12):1111-20 [PMID: 24839144]
  91. J Exp Med. 2009 Aug 31;206(9):1983-94 [PMID: 19703986]
  92. Amino Acids. 2017 Sep;49(9):1571-1585 [PMID: 28593346]
  93. FASEB J. 2014 Sep;28(9):3919-29 [PMID: 24868009]
  94. Immunity. 2015 Dec 15;43(6):1137-47 [PMID: 26680206]
  95. J Clin Invest. 2003 Aug;112(4):460-7 [PMID: 12925683]
  96. Heredity (Edinb). 2017 May;118(5):453-465 [PMID: 27925615]
  97. Nat Rev Drug Discov. 2011 Dec 16;11(1):37-51 [PMID: 22173434]
  98. Vet Res. 2018 Jul 31;49(1):68 [PMID: 30060758]
  99. Sci Rep. 2018 Jan 17;8(1):943 [PMID: 29343843]
  100. Int Immunopharmacol. 2018 Jan;54:52-59 [PMID: 29101873]
  101. Biomaterials. 2013 Aug;34(24):5969-77 [PMID: 23680363]
  102. Antimicrob Agents Chemother. 2005 May;49(5):1727-32 [PMID: 15855488]
  103. BMC Vet Res. 2016 Oct 13;12(1):231 [PMID: 27737668]
  104. Int J Pept. 2013;2013:390230 [PMID: 23554820]
  105. Front Immunol. 2017 Nov 27;8:1637 [PMID: 29230218]
  106. J Biol Chem. 2011 Sep 30;286(39):34121-30 [PMID: 21832078]
  107. Nat Rev Drug Discov. 2020 May;19(5):311-332 [PMID: 32107480]
  108. PLoS Genet. 2008 Aug 01;4(8):e1000144 [PMID: 18670650]
  109. Blood. 2001 Jun 15;97(12):3951-9 [PMID: 11389039]
  110. Nat Rev Immunol. 2016 May;16(5):321-34 [PMID: 27087664]
  111. Front Immunol. 2015 Aug 20;6:404 [PMID: 26347737]
  112. Lancet. 2020 Jan 18;395(10219):200-211 [PMID: 31954465]
  113. Chem Biol Drug Des. 2017 Dec;90(6):1155-1160 [PMID: 28581672]
  114. PLoS One. 2014 Oct 22;9(10):e111355 [PMID: 25337708]
  115. ACS Appl Mater Interfaces. 2015 Dec 30;7(51):28591-605 [PMID: 26641308]
  116. Ann Dermatol. 2018 Apr;30(2):136-142 [PMID: 29606809]
  117. Sci Rep. 2016 May 16;6:25679 [PMID: 27181680]
  118. J Control Release. 2016 May 10;229:163-171 [PMID: 27012977]
  119. Sci Rep. 2017 Jan 19;7:40874 [PMID: 28102367]
  120. Chem Rev. 2015 Feb 25;115(4):1760-846 [PMID: 25594509]
  121. Mol Biosyst. 2009 May;5(5):483-96 [PMID: 19381363]
  122. Lupus. 2011 Aug;20(9):904-11 [PMID: 21562016]
  123. EBioMedicine. 2014 Nov 1;1(1):64-71 [PMID: 25685830]
  124. Nat Rev Dis Primers. 2019 Aug 16;5(1):56 [PMID: 31420554]
  125. JAMA. 2018 Oct 02;320(13):1360-1372 [PMID: 30285183]
  126. J Infect Dis. 2017 Mar 15;215(6):975-983 [PMID: 28453851]
  127. Trends Biotechnol. 2009 Oct;27(10):582-90 [PMID: 19683819]
  128. Int J Antimicrob Agents. 2013 Feb;41(2):143-8 [PMID: 23141114]
  129. Peptides. 2003 Nov;24(11):1747-52 [PMID: 15019206]
  130. Front Chem. 2017 Aug 24;5:63 [PMID: 28971093]
  131. PLoS One. 2015 Apr 24;10(4):e0124706 [PMID: 25909853]
  132. Ann Rheum Dis. 2013 Jul;72(7):1239-48 [PMID: 23172753]
  133. J Leukoc Biol. 2005 Apr;77(4):451-9 [PMID: 15569695]
  134. Molecules. 2018 Feb 23;23(2): [PMID: 29473887]
  135. Vaccines (Basel). 2018 Sep 14;6(3): [PMID: 30223448]
  136. J Med Chem. 2018 Mar 8;61(5):2075-2086 [PMID: 29466000]
  137. Int J Endocrinol. 2014;2014:703696 [PMID: 24790601]
  138. J Control Release. 2016 Jan 28;222:1-8 [PMID: 26658071]
  139. Rheumatol Int. 2017 Sep;37(9):1551-1557 [PMID: 28455559]
  140. Trends Immunol. 2014 Sep;35(9):443-50 [PMID: 25113635]
  141. Peptides. 2006 Apr;27(4):649-60 [PMID: 16274847]
  142. Antimicrob Agents Chemother. 2017 Aug 24;61(9): [PMID: 28630199]
  143. Nature. 2001 Nov 22;414(6862):454-7 [PMID: 11719807]
  144. J Am Acad Dermatol. 2014 Mar;70(3):512-6 [PMID: 24388724]
  145. Immunology. 2013 Nov;140(3):344-51 [PMID: 23826736]
  146. Dev Comp Immunol. 2019 Mar;92:179-192 [PMID: 30452933]
  147. Ann N Y Acad Sci. 2010 Dec;1213:46-61 [PMID: 20946578]
  148. Front Vet Sci. 2019 Jul 12;6:233 [PMID: 31355218]
  149. FASEB J. 2006 Oct;20(12):2068-80 [PMID: 17012259]
  150. J Immunol. 2006 Feb 15;176(4):2455-64 [PMID: 16456005]
  151. Mol Immunol. 2014 Feb;57(2):86-92 [PMID: 24091294]
  152. Biochem J. 2018 Sep 11;475(17):2785-2799 [PMID: 30045878]
  153. BMC Evol Biol. 2015 Sep 15;15:188 [PMID: 26373713]
  154. Int Immunol. 2011 Mar;23(3):185-93 [PMID: 21393634]

Word Cloud

Created with Highcharts 10.0.0HDPsinnateimmunityimmunepeptidesinflammatorydeveloptherapeuticsinflammationresponsesHost-defensevitalcomponentsvertebratesantibacterialactivitytowardbacterialcellsoriginalfocusresearchabilitymodulateprocessesemergedonemajorfunctionshostpromisingapproachnoveltargetingreviewparticularemphasiscathelicidinfamilyrolesnaturalexaminedmanagingactivationcellularrecruitmentcytokineresponseinfectionwellcontributionsvariousdisordersautoimmunediseasesFurthermorediscusscurrenteffortssyntheticaimedrestoringbalancedysregulatedcontributediseasepathologiesCathelicidinHostDefensePeptidesInflammatorySignaling:StrikingBalancehomeostasishost-defensepeptideself-antigentoll-likereceptor

Similar Articles

Cited By