Oral administration of heat-killed Mycobacterium manresensis delays progression towards active tuberculosis in C3HeB/FeJ mice
Low-dose tolerance using heat-killed mycobacteria has been tested as a means of stopping progression towards 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-tuberculo...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-01-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.01482/full |
| _version_ | 1818306835367591936 |
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| author | Paula eCardona Paula eCardona Elena eMarzo-Escartín Elena eMarzo-Escartín Gustavo eTapia Jorge eDíaz Jorge eDíaz Vanessa eGarcía Vanessa eGarcía Ismael eVarela Ismael eVarela Cristina eVilaplana Cristina eVilaplana Pere-Joan eCardona Pere-Joan eCardona |
| author_facet | Paula eCardona Paula eCardona Elena eMarzo-Escartín Elena eMarzo-Escartín Gustavo eTapia Jorge eDíaz Jorge eDíaz Vanessa eGarcía Vanessa eGarcía Ismael eVarela Ismael eVarela Cristina eVilaplana Cristina eVilaplana Pere-Joan eCardona Pere-Joan eCardona |
| author_sort | Paula eCardona |
| collection | DOAJ |
| description | Low-dose tolerance using heat-killed mycobacteria has been tested as a means of stopping progression towards 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 two 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 two-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 active TB after ending the treatment. Overall the data suggest that the use of heat-killed M. manresensis could be a new and promising tool for avoiding active TB induction and as adjunctive to TB treatment. This supports the usefulness of generating a new kind of protection based on a complex balanced immune response focused on both destroying the bacilli and including control of an excessive inflammatory response. |
| first_indexed | 2024-12-13T06:48:48Z |
| format | Article |
| id | doaj.art-360ec7c22e0a4071af4b75565e49e21d |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-13T06:48:48Z |
| publishDate | 2016-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-360ec7c22e0a4071af4b75565e49e21d2022-12-21T23:56:12ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2016-01-01610.3389/fmicb.2015.01482167490Oral administration of heat-killed Mycobacterium manresensis delays progression towards active tuberculosis in C3HeB/FeJ micePaula eCardona0Paula eCardona1Elena eMarzo-Escartín2Elena eMarzo-Escartín3Gustavo eTapia4Jorge eDíaz5Jorge eDíaz6Vanessa eGarcía7Vanessa eGarcía8Ismael eVarela9Ismael eVarela10Cristina eVilaplana11Cristina eVilaplana12Pere-Joan eCardona13Pere-Joan eCardona14Fundació Institut Germans Trias i PujolUniversitat Autònoma de Barcelona, CIBER Enfermedades RespiratoriasFundació Institut Germans Trias i PujolUniversitat Autònoma de Barcelona, CIBER Enfermedades RespiratoriasHospital Germans Trias i PujolFundació Institut Germans Trias i PujolUniversitat Autònoma de Barcelona, CIBER Enfermedades RespiratoriasFundació Institut Germans Trias i PujolUniversitat Autònoma de Barcelona, CIBER Enfermedades RespiratoriasFundació Institut Germans Trias i PujolUniversitat Autònoma de Barcelona, CIBER Enfermedades RespiratoriasFundació Institut Germans Trias i PujolUniversitat Autònoma de Barcelona, CIBER Enfermedades RespiratoriasFundació Institut Germans Trias i PujolUniversitat Autònoma de Barcelona, CIBER Enfermedades RespiratoriasLow-dose tolerance using heat-killed mycobacteria has been tested as a means of stopping progression towards 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 two 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 two-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 active TB after ending the treatment. Overall the data suggest that the use of heat-killed M. manresensis could be a new and promising tool for avoiding active TB induction and as adjunctive to TB treatment. This supports the usefulness of generating a new kind of protection based on a complex balanced immune response focused on both destroying the bacilli and including control of an excessive inflammatory response.http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.01482/fullMiceNeutrophilsTuberculosistoleranceTregsC3HeB/FeJ |
| spellingShingle | Paula eCardona Paula eCardona Elena eMarzo-Escartín Elena eMarzo-Escartín Gustavo eTapia Jorge eDíaz Jorge eDíaz Vanessa eGarcía Vanessa eGarcía Ismael eVarela Ismael eVarela Cristina eVilaplana Cristina eVilaplana Pere-Joan eCardona Pere-Joan eCardona Oral administration of heat-killed Mycobacterium manresensis delays progression towards active tuberculosis in C3HeB/FeJ mice Frontiers in Microbiology Mice Neutrophils Tuberculosis tolerance Tregs C3HeB/FeJ |
| title | Oral administration of heat-killed Mycobacterium manresensis delays progression towards active tuberculosis in C3HeB/FeJ mice |
| title_full | Oral administration of heat-killed Mycobacterium manresensis delays progression towards active tuberculosis in C3HeB/FeJ mice |
| title_fullStr | Oral administration of heat-killed Mycobacterium manresensis delays progression towards active tuberculosis in C3HeB/FeJ mice |
| title_full_unstemmed | Oral administration of heat-killed Mycobacterium manresensis delays progression towards active tuberculosis in C3HeB/FeJ mice |
| title_short | Oral administration of heat-killed Mycobacterium manresensis delays progression towards active tuberculosis in C3HeB/FeJ mice |
| title_sort | oral administration of heat killed mycobacterium manresensis delays progression towards active tuberculosis in c3heb fej mice |
| topic | Mice Neutrophils Tuberculosis tolerance Tregs C3HeB/FeJ |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.01482/full |
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