Non-Specific Antibodies Induce Lysosomal Activation in Atlantic Salmon Macrophages Infected by Piscirickettsia salmonis
Pérez-Stuardo, Diego (Universidad Mayor. Centro de Genómica y Bioinformática)
Espinoza, Allison (Universidad Mayor. Centro de Genómica y Bioinformática)
Tapia, Sebastián (Universidad Mayor. Centro de Genómica y Bioinformática)
Morales-Reyes, Jonathan (Ictio Biotechnologies S.A. Consorcio Tecnológico de Sanidad Acuícola)
Barrientos, Claudio (Ictio Biotechnologies S.A. Consorcio Tecnológico de Sanidad Acuícola)
Vallejos Vidal, Eva Carolina (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Sandino, Ana María (Universidad de Santiago de Chile. Centro de Biotecnología Acuícola)
Spencer, Eugenio (Universidad de Santiago de Chile. Centro de Biotecnología Acuícola)
Toro-Ascuy, Daniela (Universidad Autónoma de Chile. Instituto de Ciencias Biomédicas)
Rivas-Pardo, J. Andrés (Universidad Mayor. Escuela de Biotecnología)
Reyes-López, Felipe E. (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Reyes-Cerpa, Sebastián (Universidad Mayor. Escuela de Biotecnología)

Data:	2020
Resum:	Piscirickettsia salmonis, an aggressive intracellular pathogen, is the etiological agent of salmonid rickettsial septicemia (SRS). This is a chronic multisystemic disease that generates high mortalities and large losses in Chilean salmon farming, threatening the sustainability of the salmon industry. Previous reports suggest that P. salmonis is able to survive and replicate in salmonid macrophages, inducing an anti-inflammatory environment and a limited lysosomal response that may be associated with host immune evasion mechanisms favoring bacterial survival. Current control and prophylaxis strategies against P. salmonis (based on the use of antibiotics and vaccines) have not had the expected success against infection. This makes it urgent to unravel the host-pathogen interaction to develop more effective therapeutic strategies. In this study, we evaluated the effect of treatment with IgM-beads on lysosomal activity in Atlantic salmon macrophage-enriched cell cultures infected with P. salmonis by analyzing the lysosomal pH and proteolytic ability through confocal microscopy. The impact of IgM-beads on cytotoxicity induced by P. salmonis in infected cells was evaluated by quantification of cell lysis through release of Lactate Dehydrogenase (LDH) activity. Bacterial load was determined by quantification of 16S rDNA copy number by qPCR, and counting of colony-forming units (CFU) present in the extracellular and intracellular environment. Our results suggest that stimulation with antibodies promotes lysosomal activity by lowering lysosomal pH and increasing the proteolytic activity within this organelle. Additionally, incubation with IgM-beads elicits a decrease in bacterial-induced cytotoxicity in infected Atlantic salmon macrophages and reduces the bacterial load. Overall, our results suggest that stimulation of cells infected by P. salmonis with IgM-beads reverses the modulation of the lysosomal activity induced by bacterial infection, promoting macrophage survival and bacterial elimination. This work represents a new important evidence to understand the bacterial evasion mechanisms established by P. salmonis and contribute to the development of new effective therapeutic strategies against SRS.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Macrophages ; Atlantic salmon ; IgM ; P. salmonis ; Lysosome activity
Publicat a:	Frontiers in immunology, Vol. 11 (November 2020) , art. 544718, ISSN 1664-3224

DOI: 10.3389/fimmu.2020.544718
PMID: 33281810

13 p, 3.0 MB

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