Prospects of Antimicrobial Peptides as Immunomodulators in the Treatment of Bacterial Infections

Guozhu LIANG; Shimei RUAN; Yanmei HE; Hailong YANG

doi:10.12259/j.issn.2095-610X.S20231013

Volume 44 Issue 10

Oct. 2023

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Guozhu LIANG, Shimei RUAN, Yanmei HE, Hailong YANG. Prospects of Antimicrobial Peptides as Immunomodulators in the Treatment of Bacterial Infections[J]. Journal of Kunming Medical University, 2023, 44(10): 189-195. doi: 10.12259/j.issn.2095-610X.S20231013

Citation:

Guozhu LIANG, Shimei RUAN, Yanmei HE, Hailong YANG. Prospects of Antimicrobial Peptides as Immunomodulators in the Treatment of Bacterial Infections[J]. Journal of Kunming Medical University, 2023, 44(10): 189-195. doi: 10.12259/j.issn.2095-610X.S20231013

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Prospects of Antimicrobial Peptides as Immunomodulators in the Treatment of Bacterial Infections

doi: 10.12259/j.issn.2095-610X.S20231013

School of Basic Medicine，Kunming Medical University， Kunming Yunnan 650500，China

Received Date: 2023-07-09
Available Online: 2023-09-07
Publish Date: 2023-10-25

Abstract

Abstract

Since penicillin was used to treat bacterial infectious diseases in 1928, antibiotics have saved countless patients’ lives. However, with the increase of bacterial drug resistance, the clinical treatment of bacterial infectious diseases has become increasingly difficult. Antimicrobial peptides is considered as an ideal substitute for traditional antibiotics because of its wide range of functions and low toxicity. Among them, some antimicrobial peptides with immune regulation function can regulate the innate immunity and acquired immune response of the body, directly target the immune system of the body rather than pathogenic microorganisms, thus avoiding the selection pressure on pathogenic microorganisms, and are not easily resistant to antibiotics. They have broad application value in infection treatment. This article reviews the immunomodulatory activity of antimicrobial peptides, its potential application in clinical treatment, and its limitations, so as to provide a new perspective for the development and utilization of new antibiotics.
- Bacterial infection,
- Antimicrobial peptides,
- Immune regulation

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References(69)

References

[1]	Zasloff M. Antimicrobial peptides of multicellular organisms[J]. Nature,2002,415(6870):389-395. doi: 10.1038/415389a
[2]	Hancock R E,Nijnik A,Philpott D J. Modulating immunity as a therapy for bacterial infections[J]. Nat Rev Microbiol,2012,10(4):243-254. doi: 10.1038/nrmicro2745
[3]	Hamill P,Brown K,Jenssen H,et al. Novel anti-infectives: Is host defence the answer?[J]. Curr Opin Biotechnol,2008,19(6):628-636. doi: 10.1016/j.copbio.2008.10.006
[4]	Blyth G a D,Connors L,Fodor C,et al. The network of colonic host defense peptides as an innate immune defense against enteropathogenic bacteria[J]. Front Immunol,2020,11(15):965.
[5]	Shelley J R,Davidson D J,Dorin J R. The dichotomous responses driven by β-defensins[J]. Front Immunol,2020,11(56):1176.
[6]	Wu D,Fu L,Wen W,et al. The dual antimicrobial and immunomodulatory roles of host defense peptides and their applications in animal production[J]. Anim Sci Biotechnol,2022,13(1):141. doi: 10.1186/s40104-022-00796-y
[7]	Buccini D F,Cardoso M H,Franco O L. Antimicrobial peptides and cell-penetrating peptides for treating intracellular bacterial infections[J]. Front Cell Infect Microbiol,2021,10:612931. doi: 10.3389/fcimb.2020.612931
[8]	Bowdish D M,Davidson D J,Lau Y E,et al. Impact of LL-37 on anti-infective immunity[J]. J Leukoc Biol,2005,77(4):451-459.
[9]	Brown K L,Hancock R E. Cationic host defense (antimicrobial) peptides[J]. Curr Opin Immunol,2006,18(1):24-30. doi: 10.1016/j.coi.2005.11.004
[10]	Döring Y,Libby P,Soehnlein O. Neutrophil extracellular traps participate in cardiovascular diseases:Recent experimental and clinical insights[J]. Circ Res,2020,126(9):1228-1241. doi: 10.1161/CIRCRESAHA.120.315931
[11]	Alford M A,Baquir B,Santana F L,et al. Cathelicidin host defense peptides and inflammatory signaling:Striking a balance[J]. Front Microbiol,2020,11:1902. doi: 10.3389/fmicb.2020.01902
[12]	Territo M C,Ganz T,Selsted M E,et al. Monocyte-chemotactic activity of defensins from human neutrophils[J]. J Clin Invest,1989,84(6):2017-2020. doi: 10.1172/JCI114394
[13]	Hölzl M A,Hofer J,Steinberger P,et al. Host antimicrobial proteins as endogenous immunomodulators[J]. Immunol Lett,2008,119(1-2):4-11. doi: 10.1016/j.imlet.2008.05.003
[14]	Van Harten R M,Van Woudenbergh E,Van Dijk A,et al. Cathelicidins: Immunomodulatory antimicrobials[J]. Vaccines (Basel),2018,6(3):1-23.
[15]	Zughaier S M,Shafer W M,Stephens D S. Antimicrobial peptides and endotoxin inhibit cytokine and nitric oxide release but amplify respiratory burst response in human and murine macrophages[J]. Cell Microbiol,2005,7(9):1251-1262. doi: 10.1111/j.1462-5822.2005.00549.x
[16]	Cai J,Cui X,Wang X,et al. A Novel anti-infective peptide BCCY-1 with immunomodulatory activities[J]. Front Immunol,2021,12:713960. doi: 10.3389/fimmu.2021.713960
[17]	Laman A G,Lathe R,Savinov G V,et al. Innate immunity: Bacterial cell-wall muramyl peptide targets the conserved transcription factor YB-1[J]. FEBS Lett,2015,589(15):1819-1824. doi: 10.1016/j.febslet.2015.05.028
[18]	Mookherjee N,Hancock R E. Cationic host defence peptides: Innate immune regulatory peptides as a novel approach for treating infections[J]. Cell Mol Life Sci,2007,64(7-8):922-933. doi: 10.1007/s00018-007-6475-6
[19]	Nijnik A,Hancock R. Host defence peptides: Antimicrobial and immunomodulatory activity and potential applications for tackling antibiotic-resistant infections[J]. Emerg Health Threats J,2009,2:e1.
[20]	Tjabringa G S,Ninaber D K,Drijfhout J W,et al. Human cathelicidin LL-37 is a chemoattractant for eosinophils and neutrophils that acts via formyl-peptide receptors[J]. Int Arch Allergy Immunol,2006,140(2):103-112. doi: 10.1159/000092305
[21]	De Y,Chen Q,Schmidt A P,et al. LL-37,the neutrophil granule and epithelial cell-derived cathelicidin,utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils,monocytes,and T cells[J]. J Exp Med,2000,192(7):1069-1074. doi: 10.1084/jem.192.7.1069
[22]	Niyonsaba F,Iwabuchi K,Someya A,et al. A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis[J]. Immunology,2002,106(1):20-26. doi: 10.1046/j.1365-2567.2002.01398.x
[23]	Yang D,Chen Q,Le Y,et al. Differential regulation of formyl peptide receptor-like 1 expression during the differentiation of monocytes to dendritic cells and macrophages[J]. J Immunol,2001,166(6):4092-4098. doi: 10.4049/jimmunol.166.6.4092
[24]	Lee H Y,Bae Y S. The anti-infective peptide,innate defense-regulator peptide,stimulates neutrophil chemotaxis via a formyl peptide receptor[J]. Biochem Biophys Res Commun,2008,369(2):573-578. doi: 10.1016/j.bbrc.2008.02.046
[25]	Scott M G,Dullaghan E,Mookherjee N,et al. An anti-infective peptide that selectively modulates the innate immune response[J]. Nat Biotechnol,2007,25(4):465-472. doi: 10.1038/nbt1288
[26]	Chen X,Takai T,Xie Yet al. Human antimicrobial peptide LL-37 modulates proinflammatory responses induced by cytokine milieus and double-stranded RNA in human keratinocytes[J]. Biochem Biophys Res Commun,2013,433(4):532-537. doi: 10.1016/j.bbrc.2013.03.024
[27]	Coorens M,Scheenstra M R,Veldhuizen E J,et al. Interspecies cathelicidin comparison reveals divergence in antimicrobial activity,TLR modulation,chemokine induction and regulation of phagocytosis[J]. Sci Rep,2017,7:40874. doi: 10.1038/srep40874
[28]	Bautista-Hernández L A,Gómez-Olivares J L,Buentello-Volante B,et al. Fibroblasts: The unknown sentinels eliciting immune responses against microorganisms[J]. Eur J Microbiol Immunol (Bp),2017,7(3):151-157. doi: 10.1556/1886.2017.00009
[29]	Li N,Yamasaki K,Saito R,et al. Alarmin function of cathelicidin antimicrobial peptide LL37 through IL-36γ induction in human epidermal keratinocytes[J]. J Immunol,2014,193(10):5140-5148.
[30]	Scott M G,Davidson D J,Gold M R,et al. The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses[J]. J Immunol,2002,169(7):3883-3891.
[31]	Moser M,Murphy K M. Dendritic cell regulation of TH1-TH2 development[J]. Nat Immunol,2000,1(3):199-205. doi: 10.1038/79734
[32]	Davidson D J,Currie A J,Reid G S,et al. The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization[J]. J Immunol,2004,172(2):1146-1156. doi: 10.4049/jimmunol.172.2.1146
[33]	Bandholtz L,Ekman G J,Vilhelmsson M,et al. Antimicrobial peptide LL-37 internalized by immature human dendritic cells alters their phenotype[J]. Scand J Immunol,2006,63(6):410-419. doi: 10.1111/j.1365-3083.2006.001752.x
[34]	Kim S H,Kim Y N,Jang Y S. Cutting Edge: LL-37-mediated formyl peptide receptor-2 signaling in follicular dendritic cells contributes to B cell activation in peyer's patch germinal centers[J]. J Immunol,2017,198(2):629-633. doi: 10.4049/jimmunol.1600886
[35]	Yu Y,Zhang Y,Zhang Y,et al. LL-37-induced human mast cell activation through G protein-coupled receptor MrgX2[J]. Int Immunopharmacol,2017,49:6-12. doi: 10.1016/j.intimp.2017.05.016
[36]	Gupta K,Subramanian H,Ali H. Modulation of host defense peptide-mediated human mast cell activation by LPS[J]. Innate Immun,2016,22(1):21-30. doi: 10.1177/1753425915610643
[37]	Subramanian H,Gupta K,Guo Q,et al. Mas-related gene X2 (MrgX2) is a novel G protein-coupled receptor for the antimicrobial peptide LL-37 in human mast cells: Resistance to receptor phosphorylation,desensitization,and internalization[J]. J Biol Chem,2011,286(52):44739-44749. doi: 10.1074/jbc.M111.277152
[38]	Rajakariar R,Hilliard M,Lawrence T,et al. Hematopoietic prostaglandin D2 synthase controls the onset and resolution of acute inflammation through PGD2 and 15-deoxyDelta12 14 PGJ2[J]. Proc Natl Acad Sci U S A,2007,104(52):20979-20984. doi: 10.1073/pnas.0707394104
[39]	Zhang Y Y,Yu Y Y,Zhang Y R,et al. The modulatory effect of TLR2 on LL-37-induced human mast cells activation[J]. Biochem Biophys Res Commun,2016,470(2):368-374. doi: 10.1016/j.bbrc.2016.01.037
[40]	Andrés C M C,Pérez De La Lastra J M,Juan C A,et al. The role of reactive species on innate immunity[J]. Vaccines (Basel),2022,10(10):1735. doi: 10.3390/vaccines10101735
[41]	Yang B,Good D,Mosaiab T,et al. Significance of LL-37 on immunomodulation and disease outcome[J]. Biomed Res Int,2020,2020:8349712.
[42]	Yang Y,Jing W,Qiao L,et al. A non-bactericidal cathelicidin provides prophylactic efficacy against bacterial infection by driving phagocyte influx[J]. Elife,2022,11:e72849. doi: 10.7554/eLife.72849
[43]	Jinwei C,Xin C,Tiaofei Y,et al. Characterization and functional analysis of cathelicidin-MH,a novel frog-derived peptide with anti-septicemic properties[J]. Elife,2021,10:e64411. doi: 10.7554/eLife.64411
[44]	Yeung A T,Gellatly S L,Hancock R E. Multifunctional cationic host defence peptides and their clinical applications[J]. Cell Mol Life Sci,2011,68(13):2161-2176. doi: 10.1007/s00018-011-0710-x
[45]	Mookherjee N,Anderson M A,Haagsman H P,et al. Antimicrobial host defence peptides: Functions and clinical potential[J]. Nat Rev Drug Discov,2020,19(5):311-332. doi: 10.1038/s41573-019-0058-8
[46]	Mookherjee N,Brown K L,Bowdish D M,et al. Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37[J]. J Immunol,2006,176(4):2455-2464. doi: 10.4049/jimmunol.176.4.2455
[47]	Amatngalim G D,Nijnik A,Hiemstra P S,et al. Cathelicidin peptide LL-37 modulates TREM-1 expression and inflammatory responses to microbial compounds[J]. Inflammation,2011,34(5):412-425. doi: 10.1007/s10753-010-9248-6
[48]	Shaykhiev R,Sierigk J,Herr C,et al. The antimicrobial peptide cathelicidin enhances activation of lung epithelial cells by LPS[J]. Faseb J,2010,24(12):4756-4766. doi: 10.1096/fj.09-151332
[49]	Marin M,Holani R,Shah C B,et al. Cathelicidin modulates synthesis of Toll-like Receptors (TLRs) 4 and 9 in colonic epithelium[J]. Mol Immunol,2017,91:249-258. doi: 10.1016/j.molimm.2017.09.011
[50]	Choi K Y,Napper S,Mookherjee N. Human cathelicidin LL-37 and its derivative IG-19 regulate interleukin-32-induced inflammation[J]. Immunology,2014,143(1):68-80. doi: 10.1111/imm.12291
[51]	Niyonsaba F,Madera L,Afacan N,et al. The innate defense regulator peptides IDR-HH2,IDR-1002,and IDR-1018 modulate human neutrophil functions[J]. J Leukoc Biol,2013,94(1):159-170. doi: 10.1189/jlb.1012497
[52]	Kandler K,Shaykhiev R,Kleemann P,et al. The anti-microbial peptide LL-37 inhibits the activation of dendritic cells by TLR ligands[J]. Int Immunol,2006,18(12):1729-1736. doi: 10.1093/intimm/dxl107
[53]	Nijnik A,Pistolic J,Wyatt A,et al. Human cathelicidin peptide LL-37 modulates the effects of IFN-gamma on APCs[J]. J Immunol,2009,183(9):5788-5798. doi: 10.4049/jimmunol.0901491
[54]	Hilchie A L,Wuerth K,Hancock R E. Immune modulation by multifaceted cationic host defense (antimicrobial) peptides[J]. Nat Chem Biol,2013,9(12):761-768. doi: 10.1038/nchembio.1393
[55]	Luo Y,Song Y. Mechanism of antimicrobial peptides: Antimicrobial,anti-Inflammatory and antibiofilm activities[J]. Int J Mol Sci,2021,22(21):11401. doi: 10.3390/ijms222111401
[56]	Afacan N J,Yeung A T,Pena O M,et al. Therapeutic potential of host defense peptides in antibiotic-resistant infections[J]. Curr Pharm Des,2012,18(6):807-819. doi: 10.2174/138161212799277617
[57]	Vlieghe P,Lisowski V,Martinez J,et al. Synthetic therapeutic peptides: Science and Market[J]. Drug Discov Today,2010,15(1-2):40-56. doi: 10.1016/j.drudis.2009.10.009
[58]	Duarte-Mata D I,Salinas-Carmona M C. Antimicrobial peptides’ immune modulation role in intracellular bacterial infection[J]. Front Immunol,2023,14:1119574. doi: 10.3389/fimmu.2023.1119574
[59]	Abdi M,Mirkalantari S,Amirmozafari N. Bacterial resistance to antimicrobial peptides[J]. J Pept Sci,2019,25(11):e3210.
[60]	Jia F,Wang J,Peng J,et al. D-amino acid substitution enhances the stability of antimicrobial peptide polybia-CP[J]. Acta Biochim Biophys Sin (Shanghai),2017,49(10):916-925. doi: 10.1093/abbs/gmx091
[61]	Ting D S J,Beuerman R W,Dua H S,et al. Strategies in translating the therapeutic potentials of host defense peptides[J]. Front Immunol,2020,11:983. doi: 10.3389/fimmu.2020.00983
[62]	Rounds T,Straus S K. Lipidation of antimicrobial peptides as a design strategy for future alternatives to antibiotics[J]. Int J Mol Sci,2020,21(24):9692. doi: 10.3390/ijms21249692
[63]	Mahlapuu M,Håkansson J,Ringstad L,et al. Antimicrobial peptides: An emerging category of therapeutic agents[J]. Front Cell Infect Microbiol,2016,6:194.
[64]	Braun K,Pochert A,Lindén M,et al. Membrane interactions of mesoporous silica nanoparticles as carriers of antimicrobial peptides[J]. J Colloid Interface Sci,2016,475:161-170. doi: 10.1016/j.jcis.2016.05.002
[65]	Boge L,Bysell H,Ringstad L,et al. Lipid-Based liquid crystals as carriers for antimicrobial peptides:Phase behavior and antimicrobial effect[J]. Langmuir,2016,32(17):4217-4228. doi: 10.1021/acs.langmuir.6b00338
[66]	Silva J P,Gonçalves C,Costa C,et al. Delivery of LLKKK18 loaded into self-assembling hyaluronic acid nanogel for tuberculosis treatment[J]. J Control Release,2016,235:112-124. doi: 10.1016/j.jconrel.2016.05.064
[67]	D’angelo I,Casciaro B,Miro A,et al. Overcoming barriers in Pseudomonas aeruginosa lung infections: Engineered nanoparticles for local delivery of a cationic antimicrobial peptide[J]. Colloids Surf B Biointerfaces,2015,135:717-725. doi: 10.1016/j.colsurfb.2015.08.027
[68]	Sandreschi S,Piras A M,Batoni G,et al. Perspectives on polymeric nanostructures for the therapeutic application of antimicrobial peptides[J]. Nanomedicine (Lond),2016,11(13):1729-1744. doi: 10.2217/nnm-2016-0057
[69]	Abd El-Hack M E,El-Saadony M T,Shafi M E,et al. Antimicrobial and antioxidant properties of chitosan and its derivatives and their applications: A review[J]. Int J Biol Macromol,2020,164:2726-2744. doi: 10.1016/j.ijbiomac.2020.08.153

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