Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis
Bacille Calmette-Guérin (BCG) is currently the only approved vaccine against tuberculosis (TB) and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0-80%, with the lowest efficacy rates in tropical regions where TB is most...
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| description | Bacille Calmette-Guérin (BCG) is currently the only approved vaccine against tuberculosis (TB) and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0-80%, with the lowest efficacy rates in tropical regions where TB is most prevalent. This variability is partially due to ubiquitous environmental mycobacteria (EM) found in soil and water sources, with high EM prevalence coinciding with areas of poor vaccine efficacy. In an effort to elucidate the mechanisms underlying EM interference with BCG vaccine efficacy, we exposed mice chronically to Mycobacterium avium (M. avium), a specific EM, by two different routes, the oral and intradermal route, to mimic human exposure. After intradermal BCG immunization in mice exposed to oral M. avium, we saw a significant decrease in the pro-inflammatory cytokine IFN-γ, and an increase in T regulatory cells and the immunosuppressive cytokine IL-10 compared to naïve BCG-vaccinated animals. To circumvent the immunosuppressive effect of oral M. avium exposure, we vaccinated mice by the pulmonary route with BCG. Inhaled BCG immunization rescued IFN-γ levels and increased CD4 and CD8 T cell recruitment into airways in M. avium-presensitized mice. In contrast, intradermal BCG vaccination was ineffective at T cell recruitment into the airway. Pulmonary BCG vaccination proved protective against Mtb infection regardless of previous oral M. avium exposure, compared to intradermal BCG immunization. In conclusion, our data indicate that vaccination against TB by the pulmonary route increases BCG vaccine efficacy by avoiding the immunosuppressive interference generated by chronic oral exposure to EM. This has implications in TB-burdened countries where drug resistance is on the rise and health care options are limited due to economic considerations. A successful vaccine against TB is necessary in these areas as it is both effective and economical. |
| doi_str_mv | 10.1371/journal.ppat.1005614 |
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(SNL-NM), Albuquerque, NM (United States)</creatorcontrib><description>Bacille Calmette-Guérin (BCG) is currently the only approved vaccine against tuberculosis (TB) and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0-80%, with the lowest efficacy rates in tropical regions where TB is most prevalent. This variability is partially due to ubiquitous environmental mycobacteria (EM) found in soil and water sources, with high EM prevalence coinciding with areas of poor vaccine efficacy. In an effort to elucidate the mechanisms underlying EM interference with BCG vaccine efficacy, we exposed mice chronically to Mycobacterium avium (M. avium), a specific EM, by two different routes, the oral and intradermal route, to mimic human exposure. After intradermal BCG immunization in mice exposed to oral M. avium, we saw a significant decrease in the pro-inflammatory cytokine IFN-γ, and an increase in T regulatory cells and the immunosuppressive cytokine IL-10 compared to naïve BCG-vaccinated animals. To circumvent the immunosuppressive effect of oral M. avium exposure, we vaccinated mice by the pulmonary route with BCG. Inhaled BCG immunization rescued IFN-γ levels and increased CD4 and CD8 T cell recruitment into airways in M. avium-presensitized mice. In contrast, intradermal BCG vaccination was ineffective at T cell recruitment into the airway. Pulmonary BCG vaccination proved protective against Mtb infection regardless of previous oral M. avium exposure, compared to intradermal BCG immunization. In conclusion, our data indicate that vaccination against TB by the pulmonary route increases BCG vaccine efficacy by avoiding the immunosuppressive interference generated by chronic oral exposure to EM. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Price DN, Kusewitt DF, Lino CA, McBride AA, Muttil P (2016) Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis. PLoS Pathog 12(5): e1005614. doi:10.1371/journal.ppat.1005614</rights><rights>2016 Price et al 2016 Price et al</rights><rights>2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Price DN, Kusewitt DF, Lino CA, McBride AA, Muttil P (2016) Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis. 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(SNL-NM), Albuquerque, NM (United States)</creatorcontrib><title>Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis</title><title>PLoS pathogens</title><addtitle>PLoS Pathog</addtitle><description>Bacille Calmette-Guérin (BCG) is currently the only approved vaccine against tuberculosis (TB) and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0-80%, with the lowest efficacy rates in tropical regions where TB is most prevalent. This variability is partially due to ubiquitous environmental mycobacteria (EM) found in soil and water sources, with high EM prevalence coinciding with areas of poor vaccine efficacy. In an effort to elucidate the mechanisms underlying EM interference with BCG vaccine efficacy, we exposed mice chronically to Mycobacterium avium (M. avium), a specific EM, by two different routes, the oral and intradermal route, to mimic human exposure. After intradermal BCG immunization in mice exposed to oral M. avium, we saw a significant decrease in the pro-inflammatory cytokine IFN-γ, and an increase in T regulatory cells and the immunosuppressive cytokine IL-10 compared to naïve BCG-vaccinated animals. To circumvent the immunosuppressive effect of oral M. avium exposure, we vaccinated mice by the pulmonary route with BCG. Inhaled BCG immunization rescued IFN-γ levels and increased CD4 and CD8 T cell recruitment into airways in M. avium-presensitized mice. In contrast, intradermal BCG vaccination was ineffective at T cell recruitment into the airway. Pulmonary BCG vaccination proved protective against Mtb infection regardless of previous oral M. avium exposure, compared to intradermal BCG immunization. In conclusion, our data indicate that vaccination against TB by the pulmonary route increases BCG vaccine efficacy by avoiding the immunosuppressive interference generated by chronic oral exposure to EM. This has implications in TB-burdened countries where drug resistance is on the rise and health care options are limited due to economic considerations. A successful vaccine against TB is necessary in these areas as it is both effective and economical.</description><subject>Animals</subject><subject>Antigens</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>BCG Vaccine - administration & dosage</subject><subject>BCG Vaccine - immunology</subject><subject>Biology and Life Sciences</subject><subject>Colleges & universities</subject><subject>Cytokines</subject><subject>Disease Models, Animal</subject><subject>Dosage and administration</subject><subject>Drug resistance</subject><subject>Drug therapy</subject><subject>Environmental aspects</subject><subject>Environmental Exposure - adverse effects</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Immune Tolerance - immunology</subject><subject>Immunization</subject><subject>Immunophenotyping</subject><subject>Infections</subject><subject>Intradermal injections</subject><subject>Laboratories</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microbiology</subject><subject>Mortality</subject><subject>Mycobacteria</subject><subject>Mycobacterium avium</subject><subject>Mycobacterium avium - immunology</subject><subject>Oral vaccines</subject><subject>Parasitology</subject><subject>Pathogens</subject><subject>Software</subject><subject>Spleen</subject><subject>Tropical environments</subject><subject>Tuberculosis</subject><subject>Tuberculosis, Pulmonary - immunology</subject><subject>Vaccines</subject><subject>Virology</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqVk81u1DAUhSMEoqXwBggi2IDUGfyX2NkgVVWBkUqLYFhbN44z4yqxB9splAXPjsOkVQdVQigLx_Z3z9U51s2ypxjNMeX4zYUbvIVuvtlAnGOEihKze9k-Lgo645Sz-7f-97JHIVwgxDDF5cNsj3BcUEzQfvbr3EOXL12nPVil8-jyE3tpvLO9tjFdfbxSrgYVtTeQL2xaW-11yL-buB73Hhrte-gO83qI-ZmL-aeh650Ff3WYL_p-sOYnRONsDiswNsR8OdTaq6FzwYTH2YMWuqCfTOtB9vXdyfL4w-z0_P3i-Oh0pjjBcYaxAIwq0pa0qFuhmpqwljIBiNVQCdHwhmlWccKaGlgjOGBWIqJ52zQM2oYeZM-3upvUVk7RBYl5xQtUCkQSsdgSjYMLufGmTw6kAyP_HDi_kuCjUZ2WhJSVKmhdY4YYVazmUCBelgVCuCCVSFpvp25D3etG6TGmbkd098aatVy5S8lEUTHOk8CLrYAL0cigTNRqrZy1WkWJS8IrjBP0auri3bdBhyh7E5TuOrDaDcmcIFwIwjD7N8oFr2iJydj65V_o3WlN1ApSIMa2LvlQo6g8YrwqKKn4mMP8Dip9je5NsqNbk853Cl7vFCQm6h9xBUMIcvHl83-wZ7ss27LKuxC8bm_eAiM5TtO1STlOk5ymKZU9u_2ON0XX40N_A0FoGt8</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>Price, Dominique N</creator><creator>Kusewitt, Donna F</creator><creator>Lino, Christopher A</creator><creator>McBride, Amber A</creator><creator>Muttil, Pavan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>OIOZB</scope><scope>OTOTI</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160501</creationdate><title>Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis</title><author>Price, Dominique N ; 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(SNL-NM), Albuquerque, NM (United States)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>12</volume><issue>5</issue><spage>e1005614</spage><epage>e1005614</epage><pages>e1005614-e1005614</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>Bacille Calmette-Guérin (BCG) is currently the only approved vaccine against tuberculosis (TB) and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0-80%, with the lowest efficacy rates in tropical regions where TB is most prevalent. This variability is partially due to ubiquitous environmental mycobacteria (EM) found in soil and water sources, with high EM prevalence coinciding with areas of poor vaccine efficacy. In an effort to elucidate the mechanisms underlying EM interference with BCG vaccine efficacy, we exposed mice chronically to Mycobacterium avium (M. avium), a specific EM, by two different routes, the oral and intradermal route, to mimic human exposure. After intradermal BCG immunization in mice exposed to oral M. avium, we saw a significant decrease in the pro-inflammatory cytokine IFN-γ, and an increase in T regulatory cells and the immunosuppressive cytokine IL-10 compared to naïve BCG-vaccinated animals. To circumvent the immunosuppressive effect of oral M. avium exposure, we vaccinated mice by the pulmonary route with BCG. Inhaled BCG immunization rescued IFN-γ levels and increased CD4 and CD8 T cell recruitment into airways in M. avium-presensitized mice. In contrast, intradermal BCG vaccination was ineffective at T cell recruitment into the airway. Pulmonary BCG vaccination proved protective against Mtb infection regardless of previous oral M. avium exposure, compared to intradermal BCG immunization. In conclusion, our data indicate that vaccination against TB by the pulmonary route increases BCG vaccine efficacy by avoiding the immunosuppressive interference generated by chronic oral exposure to EM. This has implications in TB-burdened countries where drug resistance is on the rise and health care options are limited due to economic considerations. A successful vaccine against TB is necessary in these areas as it is both effective and economical.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27153120</pmid><doi>10.1371/journal.ppat.1005614</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigens BASIC BIOLOGICAL SCIENCES BCG Vaccine - administration & dosage BCG Vaccine - immunology Biology and Life Sciences Colleges & universities Cytokines Disease Models, Animal Dosage and administration Drug resistance Drug therapy Environmental aspects Environmental Exposure - adverse effects Enzyme-Linked Immunosorbent Assay Female Flow Cytometry Immune Tolerance - immunology Immunization Immunophenotyping Infections Intradermal injections Laboratories Medicine and Health Sciences Mice Mice, Inbred C57BL Microbiology Mortality Mycobacteria Mycobacterium avium Mycobacterium avium - immunology Oral vaccines Parasitology Pathogens Software Spleen Tropical environments Tuberculosis Tuberculosis, Pulmonary - immunology Vaccines Virology |
| title | Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis |
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