Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice

Abstract The standard treatment for high-risk non-muscle invasive bladder cancer (BC) is the intravesical administration of live Mycobacterium bovis BCG. Previous studies suggest improving this therapy by implementing non-pathogenic mycobacteria, such as Mycobacterium brumae, and/or different vehicl...

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Autores principales:	Estela Noguera-Ortega, Rosa M. Rabanal, Elisabet Gómez-Mora, Cecilia Cabrera, Marina Luquin, Esther Julián
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Brumath Mycobacteria Treatment Splenocyte Proliferation Systemic Immune Response Regulated On Activation, Normal T Cell Expressed And Secreted (RANTES) Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a0be121d86be4456831d5804c3868ac2
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spelling	oai:doaj.org-article:a0be121d86be4456831d5804c3868ac22021-12-02T15:08:02ZIntravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice10.1038/s41598-018-33253-w2045-2322https://doaj.org/article/a0be121d86be4456831d5804c3868ac22018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33253-whttps://doaj.org/toc/2045-2322Abstract The standard treatment for high-risk non-muscle invasive bladder cancer (BC) is the intravesical administration of live Mycobacterium bovis BCG. Previous studies suggest improving this therapy by implementing non-pathogenic mycobacteria, such as Mycobacterium brumae, and/or different vehicles for mycobacteria delivery, such as an olive oil (OO)-in-water emulsion. While it has been established that BCG treatment activates the immune system, the immune effects of altering the mycobacterium and/or the preparation remain unknown. In an orthotopic murine BC model, local immune responses were assessed by measuring immune cells into the bladder and macromolecules in the urine by flow cytometry and multiplexing, respectively. Systemic immune responses were analyzed by quantifying sera anti-mycobacteria antibody levels and recall responses of ex vivo splenocytes cultured with mycobacteria antigens. In both BCG- and M. brumae-treated mice, T, NK, and NKT cell infiltration in the bladder was significantly increased. Notably, T cell infiltration was enhanced in OO-in-water emulsified mycobacteria-treated mice, and urine IL-6 and KC concentrations were elevated. Furthermore, mycobacteria treatment augmented IgG antibody production and splenocyte proliferation, especially in mice receiving OO-in-water emulsified mycobacteria. Our data demonstrate that intravesical mycobacterial treatment triggers local and systemic immune responses, which are most significant when OO-in-water emulsified mycobacteria are used.Estela Noguera-OrtegaRosa M. RabanalElisabet Gómez-MoraCecilia CabreraMarina LuquinEsther JuliánNature PortfolioarticleBrumathMycobacteria TreatmentSplenocyte ProliferationSystemic Immune ResponseRegulated On Activation, Normal T Cell Expressed And Secreted (RANTES)MedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Brumath Mycobacteria Treatment Splenocyte Proliferation Systemic Immune Response Regulated On Activation, Normal T Cell Expressed And Secreted (RANTES) Medicine R Science Q
spellingShingle	Brumath Mycobacteria Treatment Splenocyte Proliferation Systemic Immune Response Regulated On Activation, Normal T Cell Expressed And Secreted (RANTES) Medicine R Science Q Estela Noguera-Ortega Rosa M. Rabanal Elisabet Gómez-Mora Cecilia Cabrera Marina Luquin Esther Julián Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice
description	Abstract The standard treatment for high-risk non-muscle invasive bladder cancer (BC) is the intravesical administration of live Mycobacterium bovis BCG. Previous studies suggest improving this therapy by implementing non-pathogenic mycobacteria, such as Mycobacterium brumae, and/or different vehicles for mycobacteria delivery, such as an olive oil (OO)-in-water emulsion. While it has been established that BCG treatment activates the immune system, the immune effects of altering the mycobacterium and/or the preparation remain unknown. In an orthotopic murine BC model, local immune responses were assessed by measuring immune cells into the bladder and macromolecules in the urine by flow cytometry and multiplexing, respectively. Systemic immune responses were analyzed by quantifying sera anti-mycobacteria antibody levels and recall responses of ex vivo splenocytes cultured with mycobacteria antigens. In both BCG- and M. brumae-treated mice, T, NK, and NKT cell infiltration in the bladder was significantly increased. Notably, T cell infiltration was enhanced in OO-in-water emulsified mycobacteria-treated mice, and urine IL-6 and KC concentrations were elevated. Furthermore, mycobacteria treatment augmented IgG antibody production and splenocyte proliferation, especially in mice receiving OO-in-water emulsified mycobacteria. Our data demonstrate that intravesical mycobacterial treatment triggers local and systemic immune responses, which are most significant when OO-in-water emulsified mycobacteria are used.
format	article
author	Estela Noguera-Ortega Rosa M. Rabanal Elisabet Gómez-Mora Cecilia Cabrera Marina Luquin Esther Julián
author_facet	Estela Noguera-Ortega Rosa M. Rabanal Elisabet Gómez-Mora Cecilia Cabrera Marina Luquin Esther Julián
author_sort	Estela Noguera-Ortega
title	Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice
title_short	Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice
title_full	Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice
title_fullStr	Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice
title_full_unstemmed	Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice
title_sort	intravesical mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/a0be121d86be4456831d5804c3868ac2
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Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice

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