Oral Administration of Heat-Killed Mycobacterium manresensis Delays Progression toward Active Tuberculosis in C3HeB/FeJ Mice

Frontiers in Microbiology
Paula CardonaPere-Joan Cardona

Abstract

Low-dose tolerance using heat-killed mycobacteria has been tested as a means of stopping progression toward active tuberculosis (TB) lesions in a human-like murine model using C3HeB/FeJ mice. In the present study, we studied the effect of different treatment schedules with heat-killed non-tuberculous-mycobacteria (NTM) species when given orally, based on the hypothesis of generating oral tolerance. This study included M. manresensis, a new species belonging to the fortuitum group, present in drinking water. Oral treatment with M. manresensis for 2 weeks was able to induce a PPD-specific Tregs population, which has been related to a decrease in the neutrophilic infiltration found in TB lesions. Further mechanistic analysis using PPD-stimulated splenocytes links this 2-week treatment with heat-killed M. manresensis to IL-10 production and memory PPD-specific Tregs, and also to a weak PPD-specific global immune response stimulation, increasing IL-6, TNF, and IFN-γ production. In lungs, this treatment decreased the bacillary load, granulomatous infiltration and pro-inflammatory cytokines (TNF, IFN-γ, IL-6, and IL-17). Oral administration of M. manresensis during standard treatment for TB also significantly reduced the relapse of ac...Continue Reading

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Citations

Oct 14, 2016·Frontiers in Microbiology·Pere-Joan Cardona
Jul 9, 2020·Clinical and Experimental Immunology·A Ahmed, A Vyakarnam
Dec 20, 2019·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Kai Ling ChinArmando Acosta
Oct 2, 2019·Frontiers in Immunology·Paula Cardona, Pere-Joan Cardona
Jan 4, 2017·International Journal of Mycobacteriology·Nestani TukvadzePere-Joan Cardona

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Methods Mentioned

BETA
flow cytometry

Software Mentioned

GraphPad
Elements D
[UNK]
GraphPad Prism
NIS
xPONENT

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