Cystatin C: immunoregulation role in macrophages infected with Porphyromonas gingivalis
Por:
Blancas-Luciano B.E., Becker-Fauser I., Zamora-Chimal J., Jiménez-García L., Lara-Martínez R., Pérez-Torres A., del Pliego M.G., Aguirre-Benítez E.L., Fernández-Presas A.M.
Publicada:
1 ene 2024
Resumen:
Background. Periodontitis is a chronic infectious disease, characterized by an exacerbated inflammatory response and a progressive loss of the supporting tissues of the teeth. Porphyromonas gingivalis is a key etiologic agent in periodontitis. Cystatin C is an antimicrobial salivary peptide that inhibits the growth of P. gingivalis. This study aimed to evaluate the antimicrobial activity of this peptide and its effect on cytokine production, nitric oxide (NO) release, reactive oxygen species (ROS) production, and programmed cell death in human macrophages infected with P. gingivalis. Methods. Monocyte-derived macrophages generated from peripheral blood were infected with P. gingivalis (MOI 1:10) and stimulated with cystatin C (2.75 µg/ml) for 24 h. The intracellular localization of P. gingivalis and cystatin C was determined by immunofluorescence and transmission electron microscopy (TEM). The intracellular antimicrobial activity of cystatin C in macrophages was assessed by counting Colony Forming Units (CFU). ELISA assay was performed to assess inflammatory (TNFa, IL-1ß) and anti-inflammatory (IL-10) cytokines. The production of nitrites and ROS was analyzed by Griess reaction and incubation with 20,70-dichlorodihydrofluorescein diacetate (H2DCFDA), respectively. Programmed cell death was assessed with the TUNEL assay, Annexin-V, and caspase activity was also determined. Results. Our results showed that cystatin C inhibits the extracellular growth of P. gingivalis. In addition, this peptide is internalized in the infected macrophage, decreases the intracellular bacterial load, and reduces the production of inflammatory cytokines and NO. Interestingly, peptide treatment increased ROS production and substantially decreased bacterial-induced macrophage apoptosis. Conclusions. Cystatin C has antimicrobial and immuno-regulatory activity in macrophages infected with P. gingivalis. These findings highlight the importance of understanding the properties of cystatin C for its possible therapeutic use against oral infections such as periodontitis. Copyright 2024 Blancas-Luciano et al.
Filiaciones:
Blancas-Luciano B.E.:
Unidad de Posgrado, Circuito de Posgrados, Ciudad Universitaria, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
Departamento de Microbiología y Parasitologia, Facultad de Medicina, Ciudad Universitaria, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
Becker-Fauser I.:
Unidad de Investigación en Medicina Experimental, Hospital General de México, Universidad Nacional Autónoma de México, Mexico City, Mexico
Zamora-Chimal J.:
Unidad de Investigación en Medicina Experimental, Hospital General de México, Universidad Nacional Autónoma de México, Mexico City, Mexico
Jiménez-García L.:
Departamento de Biología Celular, Facultad de Ciencias, Ciudad Universitaria, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
Lara-Martínez R.:
Departamento de Biología Celular, Facultad de Ciencias, Ciudad Universitaria, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
Pérez-Torres A.:
Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
del Pliego M.G.:
Departamento de Embriología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
Aguirre-Benítez E.L.:
Departamento de Embriología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
Fernández-Presas A.M.:
Departamento de Microbiología y Parasitologia, Facultad de Medicina, Ciudad Universitaria, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
Centro de Investigación en Ciencias de la Salud, Universidad Anáhuac, Huixquilucan, Estado de México, Mexico
gold, Green Published, All Open Access; Gold Open Access
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