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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 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.

SUBMITTER: Noguera-Ortega E

PROVIDER: S-EPMC6180069 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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

Noguera-Ortega Estela E Rabanal Rosa M RM Gómez-Mora Elisabet E Cabrera Cecilia C Luquin Marina M Julián Esther E

Scientific reports 20181010 1

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 ...[more]

PMID: 30305693

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Project description:Plant growth promoting rhizobacteria Pseudomonas aeruginosa strain MF-30 isolated from maize rhizosphere was characterized for several plant growth stimulating attributes. The strain MF-30 was also evaluated for antifungal properties against Rhizoctonia solani causing banded leaf and sheath blight in maize (Zea mays L.) under in vitro conditions and was found to have higher mycelial growth suppression in the culture suspension (67.41%) followed by volatile organic compounds (62.66%) and crude extract (51.20%) in a dual plate assay. The endophytic and epiphytic colonization ability was tested using Green Fluorescent Protein (GFP)-tagging. Visualization through confocal scanning laser microscope clearly indicated that strain MF-30 colonizes the root and foliar parts of the plants. Further, the effects of seed bio-priming with P. aeruginosa MF-30 was evaluated in the induction and bioaccumulation of defense-related biomolecules, enzymes, natural antioxidants, and other changes in maize under pot trial. This not only provided protection from R. solani but also ensured growth promotion under pathogenic stress conditions in maize. The maximum concentration of hydrogen peroxide (H2O2) was reported in the root and shoot of the plants treated with R. solani alone (8.47 and 17.50 mmol mg-1 protein, respectively) compared to bioagent, P. aeruginosa MF-30 bio-primed plants (3.49 and 7.50 mmol mg-1 protein, respectively). Effects on total soluble sugar content, total protein, and total proline were also found to enhanced significantly due to inoculation of P. aeruginosa MF-30. The activities of anti-oxidative defense enzymes phenylalanine ammonia lyase (PAL), ascorbate peroxidase, peroxidase, superoxide dismutase, and catalase increased significantly in the plants bio-primed with P. aeruginosa MF-30 and subsequent foliar spray of culture suspension of MF-30 compared to pathogen alone inoculated plants. qRT-PCR analysis revealed that seed bio-priming and foliar application of P. aeruginosa MF-30 significantly increased the expression of PR-1 and PR-10 genes with the simultaneous decrease in the disease severity and lesion length in the maize plants under pathogenic stress conditions. A significant enhancement of shoot and root biomass was recorded in MF-30 bio-primed plants as compared to untreated control (p < 0.05). Significant increase in plant growth and antioxidant content, as well as decreased disease severity in the P. aeruginosa MF-30 bio-primed plants, suggested the possibility of an eco-friendly and economical means of achieving antioxidants-rich, healthier maize plants.

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Dataset Information

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

Publications

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

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