Actividad inmunomoduladora y antifúngica del péptido LL37-1 en el tratamiento de la candidiasis vulvovaginal: Un estudio in vitro e in vivo

Suarez Velandia, Maicol Mauricio

Publicación:
Actividad inmunomoduladora y antifúngica del péptido LL37-1 en el tratamiento de la candidiasis vulvovaginal: Un estudio in vitro e in vivo

dc.contributor.advisor	Muñoz Henao, Julián Esteban
dc.contributor.advisor	Cruz Baquero, Claudia Andrea
dc.contributor.author	Suarez Velandia, Maicol Mauricio
dc.date.accessioned	2025-11-11T16:00:22Z
dc.date.issued	2024-11
dc.description.abstract	Candida albicans, es el principal agente etiológico de la candidiasis vulvovaginal (VVC), una enfermedad inflamatoria del tracto genital que afecta a mujeres inmunocompetentes. En este estudio se evaluó la actividad antifúngica e inmunomoduladora del péptido LL37-1 en el tratamiento de la VVC. Este péptido es un derivado de la catelicidina humana LL37, que en estudios previos demostró un efecto antifúngico promisorio. Determinamos la toxicidad de LL37-1 en fibroblastos embrionarios murinos L929 y evaluamos su interacción con polimorfonucleares (PMN) humanos. Además, se analizó el efecto de LL37-1 en el proceso de NETosis mediante la evaluación de MPO. In vivo se cuantificó la carga fúngica de animales tratados con el péptido LL37-1, se analizó la presencia de PMN mediante inmunohistoquímica de células MPO+ y los niveles de citoquinas en el canal vaginal se midieron a través de ELISA. Demostramos que LL37-1 potencia la capacidad fagocitica, induce la muerte de levaduras en PMN e inhibe la NETosis. LL37-1 aumenta la viabilidad de PMN y no es tóxico en células murinas. Los PMN estimulados con LL37-1 aumentaron significativamente los niveles de IFN-γ. LL37-1 disminuye la carga fúngica en el canal vaginal, reduce la presencia de células MPO+ y la producción de citoquinas proinflamatorias, regulando positivamente IL-17A en VVC. Comprobamos que LL37-1 es una alternativa terapéutica promisoria para el tratamiento de la VVC, ya que disminuye la carga fúngica y mejora la inmunidad innata frente a Candida albicans.
dc.description.degreelevel	Pregrado
dc.description.degreename	Bacteriólogo(a) y Laboratorista Clínico
dc.description.tableofcontents	TABLA DE CONTENIDO 1. Introducción 10 2. Antecedentes 12 3. Objetivos 14 4. Marco Teórico 4.1. Género Candida 4.2 Factores de virulencia 4.3 Candidiasis vulvovaginal (VVC) 4.4 Factores de riesgo y síntomas de la VVC 4.5. Inmunopatología de la VVC 4.6.Tratamiento de la VVC 4.7. Catelicidina humana LL37 4.8 Propiedades antifúngicas de LL37 4.9 Propiedades inmunomoduladoras de LL37 4.10 Modificaciones estructurales del péptido LL 37 4.11 Péptido LL37-1 15 15 15 16 17 17 19 19 19 20 21 21 5. Metodología 22 5.1 Diseño metodológico 22 5.2 Materiales y métodos 5.2.1 Microorganismo 5.2.2 Péptido LL37-1 5.2.3 Viabilidad de línea celular L929 5.2.4 Ensayo de Citotoxicidad 5.2.5 Aislamiento de polimorfonucleares 5.2.6 Actividad fungicida y fagocítica de PMN 5.2.7 Viabilidad celular de PMN 5.2.8 Estimulación de PMN y NETosis 5.2.9 Inmunofluorescencia 5.2.10 Estimulación de PBMC 5.2.11 Animales experimentales 5.2.12 Modelo in vivo de Candidiasis Vulvovaginal. 5.2.13 Evaluación de la carga fúngica 5.2.14 Análisis histopatológico 5.2.15 Inmunohistoquímica de células MPO + en el canal vaginal 5.2.16 Medición de citoquinas 5.2.17 Análisis estadístico 22 22 22 23 23 23 24 24 24 25 25 25 25 26 26 27 27 27 6. Resultados 6.1 El péptido LL37-1 posee una baja toxicidad en células L929 28 28 6 6.2 Los PMN estimulados con LL37-1 poseen un mayor potencial antifúngico 6.3 LL37-1 inhibe la NETosis en neutrófilos humanos e induce IFN-γ 6.4 LL37-1 regula positivamente IL-71A e IFN-γ en PBMC humanos 6.5 LL37-1 resuelve la VVC en un modelo murino 6.6 LL37-1 modula el estado inflamatorio en VVC 29 30 32 33 35 7. Discusión 37 8. Conclusión 41 9. Bibliografía 42
dc.format.extent	47p.
dc.format.mimetype	application/pdf
dc.identifier.uri	https://repositorio.universidadmayor.edu.co/handle/unicolmayor/7255
dc.language.iso	spa
dc.publisher	Universidad Colegio Mayor de Cundinamarca
dc.publisher.faculty	Facultad de Ciencias de la Salud
dc.publisher.place	Bogota
dc.publisher.program	Bacteriología y Laboratorio Clínico
dc.relation.references	Achkar JM, Fries BC. Candida infections of the genitourinary tract. Clin Microbiol Rev. 2010 Apr;23(2):253-73.
dc.relation.references	Rathod SD, Buffler PA. Highly-cited estimates of the cumulative incidence and recurrence of vulvovaginal candidiasis are inadequately documented. BMC Womens Health. 2014 Mar 10;14(1):43.
dc.relation.references	Benedict K, Singleton AL, Jackson BR, Molinari NAM. Survey of incidence, lifetime prevalence, and treatment of self-reported vulvovaginal candidiasis, United States, 2020. BMC Womens Health. 2022 May 10;22(1):147.
dc.relation.references	Zhang X, Essmann M, Burt ET, Larsen B. Estrogen effects on Candida albicans: a potential virulence-regulating mechanism. J Infect Dis. 2000 Apr;181(4):1441-6.
dc.relation.references	Benedict K, Jackson BR, Chiller T, Beer KD. Estimation of Direct Healthcare Costs of Fungal Diseases in the United States. Clin Infect Dis. 2019 May 17;68(11):1791-1797.
dc.relation.references	Ge G, Yang Z, Li D, Zhang N, Chen B, Shi D. Distinct host immune responses in recurrent vulvovaginal candidiasis and vulvovaginal candidiasis. Front Immunol. 2022;13:959740.
dc.relation.references	Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I, Reno H, Zenilman JM, Bolan GA. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021 Jul 23;70(4):1-187.
dc.relation.references	Farr A, Effendy I, Frey Tirri B, Hof H, Mayser P, Petricevic L, Ruhnke M, Schaller M, Schaefer APA, Sustr V, Willinger B, Mendling W. Guideline: Vulvovaginal candidosis (AWMF 015/072, level S2k). Mycoses. 2021 Jun;64(6):583-602.
dc.relation.references	Richardson JP, Mogavero S, Moyes DL, Blagojevic M, Krüger T, Verma AH, Coleman BM, De La Cruz Diaz J, Schulz D, Ponde NO, Carrano G, Kniemeyer O, Wilson D, Bader O, Enoiu SI, Ho J, Kichik N, Gaffen SL, Hube B, Naglik JR. Processing of Candida albicans Ece1p Is Critical for Candidalysin Maturation and Fungal Virulence. mBio. 2018 Jan 23;9(1):e02178-17.
dc.relation.references	Moyes, David L et al. “Candidalysin is a fungal peptide toxin critical for mucosal infection.” Nature vol. 532,7597 (2016): 64-8.
dc.relation.references	Yano, Junko et al. “Novel Mechanism behind the Immunopathogenesis of Vulvovaginal Candidiasis: "Neutrophil Anergy".” Infection and immunity vol. 86,3 e00684-17.
dc.relation.references	Yano, Junko et al. “Novel Mechanism behind the Immunopathogenesis of Vulvovaginal Candidiasis: "Neutrophil Anergy".” Infection and immunity vol. 86,3 e00684-17.
dc.relation.references	Dürr, Ulrich H N et al. “LL-37, the only human member of the cathelicidin family of antimicrobial peptides.” Biochimica et biophysica acta vol. 1758,9 (2006): 1408-25.
dc.relation.references	Brogden, Kim A. “Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?.” Nature reviews. Microbiology vol. 3,3 (2005): 238-50.
dc.relation.references	De Yang 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.” The Journal of experimental medicine vol. 192,7 (2000): 1069-74.
dc.relation.references	Zhang, Xianwei et al. “The cationic peptide LL-37 binds Mac-1 (CD11b/CD18) with a low dissociation rate and promotes phagocytosis.” Biochimica et biophysica acta vol. 1864,5 (2016): 471-8.
dc.relation.references	Rosenfeld, Yosef et al. “Endotoxin (lipopolysaccharide) neutralization by innate immunity host-defense peptides. Peptide properties and plausible modes of action.” The Journal of biological chemistry vol. 281,3 (2006): 1636-43.
dc.relation.references	Conti, Heather R et al. “IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis.” Cell host & microbe vol. 20,5 (2016): 606-617.
dc.relation.references	Rossi, Diego C et al. “Therapeutic use of a cationic antimicrobial peptide from the spider Acanthoscurria gomesiana in the control of experimental candidiasis.” BMC microbiology vol. 12 28. 6 Mar. 2012
dc.relation.references	Muñoz JE, Rossi DCP, Ishida K, et al. Antifungal Activity of the Biphosphinic Cyclopalladate C7a against Candida albicans Yeast Forms In Vitro and In Vivo. Front Microbiol. 2017;8:771
dc.relation.references	Csato, M et al. “Enhancement of Candida albicans killing activity of separated human epidermal cells by alpha-melanocyte stimulating hormone.” The British journal of dermatology vol. 121,1 (1989): 145-7.
dc.relation.references	d'Enfert C, Kaune AK, Alaban LR, Chakraborty S, Cole N, Delavy M, et al. The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives. FEMS Microbiol Rev. 2021;45(3).
dc.relation.references	Doron I, Mesko M, Li XV, Kusakabe T, Leonardi I, Shaw DG, et al. Mycobiota-induced IgA antibodies regulate fungal commensalism in the gut and are dysregulated in Crohn's disease. Nat Microbiol. 2021;6(12):1493-504.
dc.relation.references	25.Silva-Dias A, Miranda IM, Branco J, Monteiro-Soares M, Pina-Vaz C, Rodrigues AG. Adhesion, biofilm formation, cell surface hydrophobicity, and antifungal planktonic susceptibility: relationship among Candida spp. Front Microbiol. 2015;6:205.
dc.relation.references	26.Scarsini M, Tomasinsig L, Arzese A, D'Este F, Oro D, Skerlavaj B. Antifungal activity of cathelicidin peptides against planktonic and biofilm cultures of Candida species isolated from vaginal infections. Peptides. 2015;71:211-21.
dc.relation.references	27.Hoyer LL, Cota E. Candida albicans Agglutinin-Like Sequence (Als) Family Vignettes: A Review of Als Protein Structure and Function. Front Microbiol. 2016;7:280.
dc.relation.references	28.Phan QT, Myers CL, Fu Y, Sheppard DC, Yeaman MR, Welch WH, et al. Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells. PLoS Biol. 2007;5(3):e64.
dc.relation.references	29.Rajendran R, Sherry L, Nile CJ, Sherriff A, Johnson EM, Hanson MF, et al. Biofilm formation is a risk factor for mortality in patients with Candida albicans bloodstream infection-Scotland, 2012-2013. Clin Microbiol Infect. 2016;22(1):87-93.
dc.relation.references	30.Chandra J, Mukherjee PK, Leidich SD, Faddoul FF, Hoyer LL, Douglas LJ, et al. Antifungal resistance of candidal biofilms formed on denture acrylic in vitro. J Dent Res. 2001;80(3):903-8.
dc.relation.references	31.Uppuluri P, Acosta Zaldivar M, Anderson MZ, Dunn MJ, Berman J, Lopez Ribot JL, et al. Candida albicans Dispersed Cells Are Developmentally Distinct from Biofilm and Planktonic Cells. mBio. 2018;9(4).
dc.relation.references	32.Noble SM, Gianetti BA, Witchley JN. Candida albicans cell-type switching and functional plasticity in the mammalian host. Nat Rev Microbiol. 2017;15(2):96-108.
dc.relation.references	33.d'Enfert C, Kaune AK, Alaban LR, Chakraborty S, Cole N, Delavy M, et al. The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives. FEMS Microbiol Rev. 2021;45(3)
dc.relation.references	34.Doron I, Mesko M, Li XV, Kusakabe T, Leonardi I, Shaw DG, et al. Mycobiota-induced IgA antibodies regulate fungal commensalism in the gut and are dysregulated in Crohn's disease. Nat Microbiol. 2021;6(12):1493-504.
dc.relation.references	35.Hoyer LL, Cota E. Candida albicans Agglutinin-Like Sequence (Als) Family Vignettes: A Review of Als Protein Structure and Function. Front Microbiol. 2016;7:280.
dc.relation.references	36.Phan QT, Myers CL, Fu Y, Sheppard DC, Yeaman MR, Welch WH, et al. Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells. PLoS Biol. 2007;5(3):e64.
dc.relation.references	37.Gow NA, Brown AJ, Odds FC. Fungal morphogenesis and host invasion. Curr Opin Microbiol. 2002;5(4):366-71.
dc.relation.references	38.Sudbery P, Gow N, Berman J. The distinct morphogenic states of Candida albicans. Trends Microbiol. 2004;12(7):317-24.
dc.relation.references	39.Pande K, Chen C, Noble SM. Passage through the mammalian gut triggers a phenotypic switch that promotes Candida albicans commensalism. Nat Genet. 2013;45(9):1088-91.
dc.relation.references	40.Sasse C, Hasenberg M, Weyler M, Gunzer M, Morschhauser J. White-opaque switching of Candida albicans allows immune evasion in an environment-dependent fashion. Eukaryot Cell. 2013;12(1):50-8.
dc.relation.references	41.Sobel JD. Vulvovaginal candidosis. Lancet. 2007;369(9577):1961-71.
dc.relation.references	42.Farr A, Effendy I, Frey Tirri B, Hof H, Mayser P, Petricevic L, et al. Guideline: Vulvovaginal candidosis (AWMF 015/072, level S2k). Mycoses. 2021;64(6):583-602.
dc.relation.references	43.Jang SJ, Lee K, Kwon B, You HJ, Ko G. Vaginal lactobacilli inhibit growth and hyphae formation of Candida albicans. Sci Rep. 2019;9(1):8121.
dc.relation.references	44.Rosentul DC, Delsing CE, Jaeger M, Plantinga TS, Oosting M, Costantini I, et al. Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis. Front Microbiol. 2014;5:483.
dc.relation.references	45.Eckert LO, Hawes SE, Stevens CE, Koutsky LA, Eschenbach DA, Holmes KK. Vulvovaginal candidiasis: clinical manifestations, risk factors, management algorithm. Obstet Gynecol. 1998;92(5):757-65.
dc.relation.references	46.Kalia N, Singh J, Kaur M. Immunopathology of Recurrent Vulvovaginal Infections: New Aspects and Research Directions. Front Immunol. 2019;10:2034.
dc.relation.references	47.Richardson JP, Mogavero S, Moyes DL, Blagojevic M, Kruger T, Verma AH, et al. Processing of Candida albicans Ece1p Is Critical for Candidalysin Maturation and Fungal Virulence. mBio. 2018;9(1).
dc.relation.references	48.Moyes DL, Runglall M, Murciano C, Shen C, Nayar D, Thavaraj S, et al. A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in epithelial cells. Cell Host Microbe. 2010;8(3):225-35.
dc.relation.references	49.Willems HME, Ahmed SS, Liu J, Xu Z, Peters BM. Vulvovaginal Candidiasis: A Current Understanding and Burning Questions. J Fungi (Basel). 2020;6(1).
dc.relation.references	50.Gow NA, van de Veerdonk FL, Brown AJ, Netea MG. Candida albicans morphogenesis and host defence: discriminating invasion from colonization. Nat Rev Microbiol. 2011;10(2):112-22.
dc.relation.references	51.Conti HR, Bruno VM, Childs EE, Daugherty S, Hunter JP, Mengesha BG, et al. IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis. Cell Host Microbe. 2016;20(5):606-17.
dc.relation.references	52.Rosentul DC, Delsing CE, Jaeger M, et al. Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis. Front Microbiol. 2014;5:483.
dc.relation.references	53.Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532-1535.
dc.relation.references	54.Branzk N, Lubojemska A, Hardison SE, et al. Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens. Nat Immunol. 2014;15(11):1017-1025.
dc.relation.references	55.Zambrano F, Melo A, Rivera-Concha R, Schulz M, Uribe P, Fonseca-Salamanca F, Ossa X, Taubert A, Hermosilla C, Sánchez R. High Presence of NETotic Cells and Neutrophil Extracellular Traps in Vaginal Discharges of Women with Vaginitis: An Exploratory Study. Cells. 2022; 11(20):3185.
dc.relation.references	56.Pappas, Peter G et al. “Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America vol. 62,4 (2016): e1-50.
dc.relation.references	57.Nyirjesy P, Brookhart C, Lazenby G, Schwebke J, Sobel JD. Vulvovaginal Candidiasis: A Review of the Evidence for the 2021 Centers for Disease Control and Prevention of Sexually Transmitted Infections Treatment Guidelines. Clin Infect Dis. 2022 Apr 13;74(Suppl_2):S162-S168.
dc.relation.references	58.Pappas, Peter G et al. “Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America vol. 48,5 (2009): 503-35.
dc.relation.references	59.Donders, Gilbert et al. “Management of recurrent vulvovaginal candidosis: Narrative review of the literature and European expert panel opinion.” Frontiers in cellular and infection microbiology vol. 12 934353. 9 Sep. 2022.
dc.relation.references	60.Pappas PG, Lionakis MS, Arendrup MC, Ostrosky-Zeichner L, Kullberg BJ. Invasive candidiasis. Nat Rev Dis Primers. 2018;4:18026.
dc.relation.references	61.Rossi DC, Munoz JE, Carvalho DD, Belmonte R, Faintuch B, Borelli P, et al. Therapeutic use of a cationic antimicrobial peptide from the spider Acanthoscurria gomesiana in the control of experimental candidiasis. BMC Microbiol. 2012;12:28.
dc.relation.references	62.Munoz JE, Rossi DCP, Ishida K, Spadari CC, Melhem MSC, Garcia DM, et al. Antifungal Activity of the Biphosphinic Cyclopalladate C7a against Candida albicans Yeast Forms In Vitro and In Vivo. Front Microbiol. 2017;8:771.
dc.relation.references	63.Larrick JW, Hirata M, Balint RF, Lee J, Zhong J, Wright SC. Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect Immun. 1995;63(4):1291-1297.
dc.relation.references	64.Larrick JW, Hirata M, Balint RF, Lee J, Zhong J, Wright SC. Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect Immun. 1995;63(4):1291-1297.
dc.relation.references	65.Oren Z, Lerman JC, Gudmundsson GH, Agerberth B, Shai Y. Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity. Biochem J. 1999;341 ( Pt 3)(Pt 3):501-513.
dc.relation.references	66.Durr UH, Sudheendra US, Ramamoorthy A. LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim Biophys Acta. 2006;1758(9):1408-25.
dc.relation.references	67.Burton, Matthew F, and Patrick G Steel. “The chemistry and biology of LL-37.” Natural product reports vol. 26,12 (2009): 1572-84.
dc.relation.references	68.Hsu, Chun-Min et al. “Candida albicans Sfp1 Is Involved in the Cell Wall and Endoplasmic Reticulum Stress Responses Induced by Human Antimicrobial Peptide LL-37.” International journal of molecular sciences vol. 22,19 10633. 30 Sep. 2021
dc.relation.references	69.Tsai, Pei-Wen et al. “Human antimicrobial peptide LL-37 inhibits adhesion of Candida albicans by interacting with yeast cell-wall carbohydrates.” PloS one vol. 6,3 e17755. 14 Mar. 2011
dc.relation.references	70.Scheenstra MR, van den Belt M, Tjeerdsma-van Bokhoven JLM, et al. Cathelicidins PMAP-36, LL-37 and CATH-2 are similar peptides with different modes of action. Sci Rep. 2019;9(1):4780.
dc.relation.references	71.Luo, Yu et al. “The Naturally Occurring Host Defense Peptide, LL-37, and Its Truncated Mimetics KE-18 and KR-12 Have Selected Biocidal and Antibiofilm Activities Against Candida albicans, Staphylococcus aureus, and Escherichia coli In vitro.” Frontiers in microbiology vol. 8 544. 31 Mar. 2017
dc.relation.references	72.Yang, Binbin et al. “Significance of LL-37 on Immunomodulation and Disease Outcome.” BioMed research international vol. 2020 8349712. 16 May. 2020
dc.relation.references	73.De Yang 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.” The Journal of experimental medicine vol. 192,7 (2000): 1069-74.
dc.relation.references	74.Scott, Monisha G et al. “The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses.” Journal of immunology (Baltimore, Md. : 1950) vol. 169,7 (2002): 3883-91.
dc.relation.references	75.Cao, Yujie et al. “LL-37 promotes neutrophil extracellular trap formation in chronic rhinosinusitis with nasal polyps.” Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology vol. 49,7 (2019): 990-999.
dc.relation.references	76.Kim, Sae-Hae et al. “Antimicrobial peptide LL-37 promotes antigen-specific immune responses in mice by enhancing Th17-skewed mucosal and systemic immunities.” European journal of immunology vol. 45,5 (2015): 1402-13.
dc.relation.references	77.Tsai PW, Yang CY, Chang HT, Lan CY. Human antimicrobial peptide LL-37 inhibits adhesion of Candida albicans by interacting with yeast cell-wall carbohydrates. PLoS One. 2011;6(3):e17755.
dc.relation.references	78.Rodríguez, Esaú E et al. “Comparing the copper binding features of alpha and beta synucleins.” Journal of inorganic biochemistry vol. 229 (2022): 111715.
dc.relation.references	79.Gazendam, Roel P et al. “Human Neutrophils Use Different Mechanisms To Kill Aspergillus fumigatus Conidia and Hyphae: Evidence from Phagocyte Defects.” Journal of immunology (Baltimore, Md. : 1950) vol. 196,3 (2016): 1272-83.
dc.relation.references	80.Unger, Lucas et al. “Candida albicans induces neutrophil extracellular traps and leucotoxic hypercitrullination via candidalysin.” EMBO reports vol. 24,11 (2023): e57571.
dc.relation.references	81.Peña Agudelo, Jorge A et al. “Mitochondrial Peptide Humanin Facilitates Chemoresistance in Glioblastoma Cells.” Cancers vol. 15,16 4061. 11 Aug. 2023
dc.relation.references	82.Consuegra-Asprilla JM, Rodríguez-Echeverri C, Posada DH, Gómez BL, González Á. Patients with recurrent vulvovaginal candidiasis exhibit a decrease in both the fungicidal activity of neutrophils and the proliferation of peripheral blood mononuclear cells. Mycoses. 2024;67(4):e13720.
dc.relation.references	83.Saffarzadeh M, Juenemann C, Queisser MA, et al. Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones. PLoS One. 2012;7(2):e32366.
dc.relation.references	84.Gozalbo, Daniel et al. “Role of IFN-gamma in immune responses to Candida albicans infections.” Frontiers in bioscience (Landmark edition) vol. 19,8 1279-90. 1 Jun. 2014
dc.relation.references	85.Stevenhagen A, van Furth R. Interferon-gamma activates the oxidative killing of Candida albicans by human granulocytes. Clin Exp Immunol. 1993;91(1):170-175.
dc.relation.references	86.Satora M, Grunwald A, Zaremba B, Frankowska K, Żak K, Tarkowski R, Kułak K. Treatment of Vulvovaginal Candidiasis—An Overview of Guidelines and the Latest Treatment Methods. Journal of Clinical Medicine. 2023; 12(16):5376.
dc.relation.references	87.Willems, Hubertine M E et al. “Vulvovaginal Candidiasis: A Current Understanding and Burning Questions.” Journal of fungi (Basel, Switzerland) vol. 6,1 27. 25 Feb. 2020
dc.relation.references	88.Nuijens T., Piva E., Kruijtzer J.A.W., Rijkers D.T.S., Liskamp R.M.J., Quaedflieg P.J.L.M. Enzymatic C-terminal amidation of amino acids and peptides. Tetrahedron Lett. 2012;53:3777–3779.
dc.relation.references	89.Coombe, D R, and W C Kett. “Heparan sulfate-protein interactions: therapeutic potential through structure-function insights.” Cellular and molecular life sciences : CMLS vol. 62,4 (2005): 410-24.
dc.relation.references	90.Sanderson, R D, and M Bernfield. “Molecular polymorphism of a cell surface proteoglycan: distinct structures on simple and stratified epithelia.” Proceedings of the National Academy of Sciences of the United States of America vol. 85,24 (1988): 9562-6.
dc.relation.references	91.Boink MA, Roffel S, Nazmi K, Bolscher JGM, Veerman ECI, Gibbs S. Saliva-Derived Host Defense Peptides Histatin1 and LL-37 Increase Secretion of Antimicrobial Skin and Oral Mucosa Chemokine CCL20 in an IL-1α-Independent Manner. J Immunol Res. 2017;2017:3078194.
dc.relation.references	91.Boink MA, Roffel S, Nazmi K, Bolscher JGM, Veerman ECI, Gibbs S. Saliva-Derived Host Defense Peptides Histatin1 and LL-37 Increase Secretion of Antimicrobial Skin and Oral Mucosa Chemokine CCL20 in an IL-1α-Independent Manner. J Immunol Res. 2017;2017:3078194.
dc.relation.references	93.Radic, Marko, and Sylviane Muller. “LL-37, a Multi-Faceted Amphipathic Peptide Involved in NETosis.” Cells vol. 11,15 2463. 8 Aug. 2022
dc.relation.references	94.Hu Z, Murakami T, Suzuki K, et al. Antimicrobial cathelicidin peptide LL-37 inhibits the pyroptosis of macrophages and improves the survival of polybacterial septic mice. Int Immunol. 2016;28(5):245-253.
dc.relation.references	95.Yano J, Fidel PL Jr. Impaired neutrophil extracellular trap-forming capacity contributes to susceptibility to chronic vaginitis in a mouse model of vulvovaginal candidiasis. Infect Immun. 2024;92(3):e0035023.
dc.relation.references	96.Radic M, Muller S. LL-37, a Multi-Faceted Amphipathic Peptide Involved in NETosis. Cells. 2022;11(15):2463.
dc.relation.references	97.Rosentul DC, Delsing CE, Jaeger M, et al. Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis. Front Microbiol. 2014;5:483.
dc.relation.references	98.Li J, Casanova JL, Puel A. Mucocutaneous IL-17 immunity in mice and humans: host defense vs. excessive inflammation. Mucosal Immunol 2018; 11:581–9.
dc.relation.references	99.Xan de Veerdonk FL, Gresnigt MS, Kullberg BJ. et al. Th17 responses and host defense against microorganisms: an overview. BMB Rep 2009;42:776–87.
dc.relation.references	Peters BM, Coleman BM, Willems HME, et al. The Interleukin (IL) 17R/IL-22R Signaling Axis Is Dispensable for Vulvovaginal Candidiasis Regardless of Estrogen Status. J Infect Dis. 2020;221(9):1554-1563.
dc.relation.references	Peters BM, Coleman BM, Willems HME, et al. The Interleukin (IL) 17R/IL-22R Signaling Axis Is Dispensable for Vulvovaginal Candidiasis Regardless of Estrogen Status. J Infect Dis. 2020;221(9):1554-1563.
dc.rights	Al consultar y hacer uso de este recurso, está aceptando las condiciones de uso establecidas por los autores.
dc.rights.license	Atribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)
dc.rights.uri	https://creativecommons.org/licenses/by-nc-sa/4.0/
dc.subject.proposal	Candidiasis vulvovaginal
dc.subject.proposal	Neutrófilos
dc.subject.proposal	Catelicidina humana
dc.subject.proposal	Actividad inmunomoduladora
dc.subject.proposal	Péptidos antimicrobianos
dc.subject.proposal	Candida albicans
dc.title	Actividad inmunomoduladora y antifúngica del péptido LL37-1 en el tratamiento de la candidiasis vulvovaginal: Un estudio in vitro e in vivo
dc.type	Trabajo de grado - Pregrado
dc.type.coar	http://purl.org/coar/resource_type/c_7a1f
dc.type.coarversion	http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.content	Text
dc.type.driver	info:eu-repo/semantics/bachelorThesis
dc.type.redcol	http://purl.org/redcol/resource_type/TP
dc.type.version	info:eu-repo/semantics/publishedVersion
dspace.entity.type	Publication