Nasal Acai polysaccharides potentiate innate immunity to protect against pulmonary Francisella tularensis and Burkholderia pseudomallei Infections
Pulmonary Francisella tularensis and Burkholderia pseudomallei infections are highly lethal in untreated patients, and current antibiotic regimens are not always effective. Activating the innate immune system provides an alternative means of treating infection and can also complement antibiotic ther...
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| Veröffentlicht in: | PLoS pathogens 2012-03, Vol.8 (3), p.e1002587 |
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| creator | Skyberg, Jerod A Rollins, MaryClare F Holderness, Jeff S Marlenee, Nicole L Schepetkin, Igor A Goodyear, Andrew Dow, Steven W Jutila, Mark A Pascual, David W |
| description | Pulmonary Francisella tularensis and Burkholderia pseudomallei infections are highly lethal in untreated patients, and current antibiotic regimens are not always effective. Activating the innate immune system provides an alternative means of treating infection and can also complement antibiotic therapies. Several natural agonists were screened for their ability to enhance host resistance to infection, and polysaccharides derived from the Acai berry (Acai PS) were found to have potent abilities as an immunotherapeutic to treat F. tularensis and B. pseudomallei infections. In vitro, Acai PS impaired replication of Francisella in primary human macrophages co-cultured with autologous NK cells via augmentation of NK cell IFN-γ. Furthermore, Acai PS administered nasally before or after infection protected mice against type A F. tularensis aerosol challenge with survival rates up to 80%, and protection was still observed, albeit reduced, when mice were treated two days post-infection. Nasal Acai PS administration augmented intracellular expression of IFN-γ by NK cells in the lungs of F. tularensis-infected mice, and neutralization of IFN-γ ablated the protective effect of Acai PS. Likewise, nasal Acai PS treatment conferred protection against pulmonary infection with B. pseudomallei strain 1026b. Acai PS dramatically reduced the replication of B. pseudomallei in the lung and blocked bacterial dissemination to the spleen and liver. Nasal administration of Acai PS enhanced IFN-γ responses by NK and γδ T cells in the lungs, while neutralization of IFN-γ totally abrogated the protective effect of Acai PS against pulmonary B. pseudomallei infection. Collectively, these results demonstrate Acai PS is a potent innate immune agonist that can resolve F. tularensis and B. pseudomallei infections, suggesting this innate immune agonist has broad-spectrum activity against virulent intracellular pathogens. |
| doi_str_mv | 10.1371/journal.ppat.1002587 |
| format | Article |
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Activating the innate immune system provides an alternative means of treating infection and can also complement antibiotic therapies. Several natural agonists were screened for their ability to enhance host resistance to infection, and polysaccharides derived from the Acai berry (Acai PS) were found to have potent abilities as an immunotherapeutic to treat F. tularensis and B. pseudomallei infections. In vitro, Acai PS impaired replication of Francisella in primary human macrophages co-cultured with autologous NK cells via augmentation of NK cell IFN-γ. Furthermore, Acai PS administered nasally before or after infection protected mice against type A F. tularensis aerosol challenge with survival rates up to 80%, and protection was still observed, albeit reduced, when mice were treated two days post-infection. Nasal Acai PS administration augmented intracellular expression of IFN-γ by NK cells in the lungs of F. tularensis-infected mice, and neutralization of IFN-γ ablated the protective effect of Acai PS. Likewise, nasal Acai PS treatment conferred protection against pulmonary infection with B. pseudomallei strain 1026b. Acai PS dramatically reduced the replication of B. pseudomallei in the lung and blocked bacterial dissemination to the spleen and liver. Nasal administration of Acai PS enhanced IFN-γ responses by NK and γδ T cells in the lungs, while neutralization of IFN-γ totally abrogated the protective effect of Acai PS against pulmonary B. pseudomallei infection. Collectively, these results demonstrate Acai PS is a potent innate immune agonist that can resolve F. tularensis and B. pseudomallei infections, suggesting this innate immune agonist has broad-spectrum activity against virulent intracellular pathogens.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1002587</identifier><identifier>PMID: 22438809</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject><![CDATA[Administration, Intranasal ; Aerosols ; Animals ; Antibiotics ; Arecaceae - chemistry ; Berries ; Biological & chemical terrorism ; Biology ; Burkholderia pseudomallei ; Burkholderia pseudomallei - drug effects ; Burkholderia pseudomallei - immunology ; Cell culture ; Colleges & universities ; Cytotoxicity ; Disease Models, Animal ; Experiments ; Female ; Francisella tularensis ; Francisella tularensis - drug effects ; Francisella tularensis - immunology ; Health aspects ; Immune system ; Immunity, Innate - drug effects ; Immunology ; Infections ; Interferon-gamma - metabolism ; Killer Cells, Natural - drug effects ; Killer Cells, Natural - immunology ; Killer Cells, Natural - metabolism ; Longevity - drug effects ; Lung - drug effects ; Lung - immunology ; Lung - metabolism ; Macrophages - drug effects ; Macrophages - immunology ; Macrophages - metabolism ; Melioidosis - immunology ; Melioidosis - prevention & control ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mortality ; Neutralization ; Physiological aspects ; Plant Extracts - administration & dosage ; Plant Extracts - pharmacology ; Pneumonia - drug therapy ; Pneumonia - immunology ; Pneumonia - microbiology ; Polysaccharides ; Polysaccharides - administration & dosage ; Polysaccharides - isolation & purification ; Polysaccharides - pharmacology ; Saccharides ; Survival ; Tularemia ; Tularemia - immunology ; Tularemia - prevention & control ; Virulence (Microbiology)]]></subject><ispartof>PLoS pathogens, 2012-03, Vol.8 (3), p.e1002587</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Skyberg et al. 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: Skyberg JA, Rollins MF, Holderness JS, Marlenee NL, Schepetkin IA, et al. (2012) Nasal Acai Polysaccharides Potentiate Innate Immunity to Protect against Pulmonary Francisella tularensis and Burkholderia pseudomallei Infections. PLoS Pathog 8(3): e1002587. doi:10.1371/journal.ppat.1002587</rights><rights>Skyberg et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c660t-78b9dce64623d1e4c05d355ae2a16b80aea0deca0cf815d5a27a7a8e97a7dda53</citedby><cites>FETCH-LOGICAL-c660t-78b9dce64623d1e4c05d355ae2a16b80aea0deca0cf815d5a27a7a8e97a7dda53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305411/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305411/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22438809$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>DeLeo, Frank R.</contributor><creatorcontrib>Skyberg, Jerod A</creatorcontrib><creatorcontrib>Rollins, MaryClare F</creatorcontrib><creatorcontrib>Holderness, Jeff S</creatorcontrib><creatorcontrib>Marlenee, Nicole L</creatorcontrib><creatorcontrib>Schepetkin, Igor A</creatorcontrib><creatorcontrib>Goodyear, Andrew</creatorcontrib><creatorcontrib>Dow, Steven W</creatorcontrib><creatorcontrib>Jutila, Mark A</creatorcontrib><creatorcontrib>Pascual, David W</creatorcontrib><title>Nasal Acai polysaccharides potentiate innate immunity to protect against pulmonary Francisella tularensis and Burkholderia pseudomallei Infections</title><title>PLoS pathogens</title><addtitle>PLoS Pathog</addtitle><description>Pulmonary Francisella tularensis and Burkholderia pseudomallei infections are highly lethal in untreated patients, and current antibiotic regimens are not always effective. Activating the innate immune system provides an alternative means of treating infection and can also complement antibiotic therapies. Several natural agonists were screened for their ability to enhance host resistance to infection, and polysaccharides derived from the Acai berry (Acai PS) were found to have potent abilities as an immunotherapeutic to treat F. tularensis and B. pseudomallei infections. In vitro, Acai PS impaired replication of Francisella in primary human macrophages co-cultured with autologous NK cells via augmentation of NK cell IFN-γ. Furthermore, Acai PS administered nasally before or after infection protected mice against type A F. tularensis aerosol challenge with survival rates up to 80%, and protection was still observed, albeit reduced, when mice were treated two days post-infection. Nasal Acai PS administration augmented intracellular expression of IFN-γ by NK cells in the lungs of F. tularensis-infected mice, and neutralization of IFN-γ ablated the protective effect of Acai PS. Likewise, nasal Acai PS treatment conferred protection against pulmonary infection with B. pseudomallei strain 1026b. Acai PS dramatically reduced the replication of B. pseudomallei in the lung and blocked bacterial dissemination to the spleen and liver. Nasal administration of Acai PS enhanced IFN-γ responses by NK and γδ T cells in the lungs, while neutralization of IFN-γ totally abrogated the protective effect of Acai PS against pulmonary B. pseudomallei infection. Collectively, these results demonstrate Acai PS is a potent innate immune agonist that can resolve F. tularensis and B. pseudomallei infections, suggesting this innate immune agonist has broad-spectrum activity against virulent intracellular pathogens.</description><subject>Administration, Intranasal</subject><subject>Aerosols</subject><subject>Animals</subject><subject>Antibiotics</subject><subject>Arecaceae - chemistry</subject><subject>Berries</subject><subject>Biological & chemical terrorism</subject><subject>Biology</subject><subject>Burkholderia pseudomallei</subject><subject>Burkholderia pseudomallei - drug effects</subject><subject>Burkholderia pseudomallei - immunology</subject><subject>Cell culture</subject><subject>Colleges & universities</subject><subject>Cytotoxicity</subject><subject>Disease Models, Animal</subject><subject>Experiments</subject><subject>Female</subject><subject>Francisella tularensis</subject><subject>Francisella tularensis - drug effects</subject><subject>Francisella tularensis - immunology</subject><subject>Health aspects</subject><subject>Immune system</subject><subject>Immunity, Innate - drug effects</subject><subject>Immunology</subject><subject>Infections</subject><subject>Interferon-gamma - metabolism</subject><subject>Killer Cells, Natural - drug effects</subject><subject>Killer Cells, Natural - immunology</subject><subject>Killer Cells, Natural - metabolism</subject><subject>Longevity - drug effects</subject><subject>Lung - drug effects</subject><subject>Lung - immunology</subject><subject>Lung - metabolism</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Melioidosis - immunology</subject><subject>Melioidosis - prevention & control</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Mortality</subject><subject>Neutralization</subject><subject>Physiological aspects</subject><subject>Plant Extracts - administration & dosage</subject><subject>Plant Extracts - pharmacology</subject><subject>Pneumonia - drug therapy</subject><subject>Pneumonia - immunology</subject><subject>Pneumonia - microbiology</subject><subject>Polysaccharides</subject><subject>Polysaccharides - administration & dosage</subject><subject>Polysaccharides - isolation & purification</subject><subject>Polysaccharides - pharmacology</subject><subject>Saccharides</subject><subject>Survival</subject><subject>Tularemia</subject><subject>Tularemia - immunology</subject><subject>Tularemia - prevention & control</subject><subject>Virulence (Microbiology)</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqVk81u1DAQxyMEoqXwBggicUAcdrFjJ3EuSEtFYaWqSHycrYk92bo4drAdRF-DJ8bbbqsu6gX5MPb4N__5kKYonlOypKylby_8HBzY5TRBWlJCqlq0D4pDWtds0bKWP7xzPyiexHhBCKeMNo-Lg6riTAjSHRZ_ziCCLVcKTDl5exlBqXMIRmPM74QuGUhYGueuzDjOzqTLMvlyCvlbpRI2YFxM5TTb0TsIl-VJAKdMRGuhTLOFgC6aWILT5fs5_Dj3VmMwUE4RZ-1HsBZNuXZDVjPexafFowFsxGc7e1R8P_nw7fjT4vTzx_Xx6nShmoakRSv6TitseFMxTZErUmtW14AV0KYXBBCIRgVEDYLWuoaqhRYEdtloDTU7Kl5e607WR7kbZ5S0Eh0RXBCSifU1oT1cyCmYMbcnPRh55fBhIyEkoyzKXjRdNai-o63iiEKoqkcOPRkUVzWjWevdLtvcj5gLdymA3RPd_3HmXG78L8kYqTndCrzeCQT_c8aY5Gii2g7ZoZ-j7DgRrBaiyeSrf8j7m9tRG8j1Gzf4nFZtNeWKEc5I21VbankPlY_G0SjvcDDZvxfwZi8gMwl_pw3MMcr11y__wZ7ts_yaVcHHGHC4HR0lcrsQN03K7ULI3ULksBd3x34bdLMB7C9Oqwvp</recordid><startdate>20120301</startdate><enddate>20120301</enddate><creator>Skyberg, Jerod A</creator><creator>Rollins, MaryClare F</creator><creator>Holderness, Jeff S</creator><creator>Marlenee, Nicole L</creator><creator>Schepetkin, Igor A</creator><creator>Goodyear, Andrew</creator><creator>Dow, Steven W</creator><creator>Jutila, Mark A</creator><creator>Pascual, David W</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>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120301</creationdate><title>Nasal Acai polysaccharides potentiate innate immunity to protect against pulmonary Francisella tularensis and Burkholderia pseudomallei Infections</title><author>Skyberg, Jerod A ; Rollins, MaryClare F ; Holderness, Jeff S ; Marlenee, Nicole L ; Schepetkin, Igor A ; Goodyear, Andrew ; Dow, Steven W ; Jutila, Mark A ; Pascual, David W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c660t-78b9dce64623d1e4c05d355ae2a16b80aea0deca0cf815d5a27a7a8e97a7dda53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Administration, Intranasal</topic><topic>Aerosols</topic><topic>Animals</topic><topic>Antibiotics</topic><topic>Arecaceae - 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Activating the innate immune system provides an alternative means of treating infection and can also complement antibiotic therapies. Several natural agonists were screened for their ability to enhance host resistance to infection, and polysaccharides derived from the Acai berry (Acai PS) were found to have potent abilities as an immunotherapeutic to treat F. tularensis and B. pseudomallei infections. In vitro, Acai PS impaired replication of Francisella in primary human macrophages co-cultured with autologous NK cells via augmentation of NK cell IFN-γ. Furthermore, Acai PS administered nasally before or after infection protected mice against type A F. tularensis aerosol challenge with survival rates up to 80%, and protection was still observed, albeit reduced, when mice were treated two days post-infection. Nasal Acai PS administration augmented intracellular expression of IFN-γ by NK cells in the lungs of F. tularensis-infected mice, and neutralization of IFN-γ ablated the protective effect of Acai PS. Likewise, nasal Acai PS treatment conferred protection against pulmonary infection with B. pseudomallei strain 1026b. Acai PS dramatically reduced the replication of B. pseudomallei in the lung and blocked bacterial dissemination to the spleen and liver. Nasal administration of Acai PS enhanced IFN-γ responses by NK and γδ T cells in the lungs, while neutralization of IFN-γ totally abrogated the protective effect of Acai PS against pulmonary B. pseudomallei infection. Collectively, these results demonstrate Acai PS is a potent innate immune agonist that can resolve F. tularensis and B. pseudomallei infections, suggesting this innate immune agonist has broad-spectrum activity against virulent intracellular pathogens.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22438809</pmid><doi>10.1371/journal.ppat.1002587</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1289084800 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central Open Access; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Administration, Intranasal Aerosols Animals Antibiotics Arecaceae - chemistry Berries Biological & chemical terrorism Biology Burkholderia pseudomallei Burkholderia pseudomallei - drug effects Burkholderia pseudomallei - immunology Cell culture Colleges & universities Cytotoxicity Disease Models, Animal Experiments Female Francisella tularensis Francisella tularensis - drug effects Francisella tularensis - immunology Health aspects Immune system Immunity, Innate - drug effects Immunology Infections Interferon-gamma - metabolism Killer Cells, Natural - drug effects Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Longevity - drug effects Lung - drug effects Lung - immunology Lung - metabolism Macrophages - drug effects Macrophages - immunology Macrophages - metabolism Melioidosis - immunology Melioidosis - prevention & control Mice Mice, Inbred BALB C Mice, Inbred C57BL Mortality Neutralization Physiological aspects Plant Extracts - administration & dosage Plant Extracts - pharmacology Pneumonia - drug therapy Pneumonia - immunology Pneumonia - microbiology Polysaccharides Polysaccharides - administration & dosage Polysaccharides - isolation & purification Polysaccharides - pharmacology Saccharides Survival Tularemia Tularemia - immunology Tularemia - prevention & control Virulence (Microbiology) |
| title | Nasal Acai polysaccharides potentiate innate immunity to protect against pulmonary Francisella tularensis and Burkholderia pseudomallei Infections |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T12%3A50%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Nasal%20Acai%20polysaccharides%20potentiate%20innate%20immunity%20to%20protect%20against%20pulmonary%20Francisella%20tularensis%20and%20Burkholderia%20pseudomallei%20Infections&rft.jtitle=PLoS%20pathogens&rft.au=Skyberg,%20Jerod%20A&rft.date=2012-03-01&rft.volume=8&rft.issue=3&rft.spage=e1002587&rft.pages=e1002587-&rft.issn=1553-7374&rft.eissn=1553-7374&rft_id=info:doi/10.1371/journal.ppat.1002587&rft_dat=%3Cgale_plos_%3EA304307920%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1289084800&rft_id=info:pmid/22438809&rft_galeid=A304307920&rft_doaj_id=oai_doaj_org_article_b8692fcb917c4ee88c2be4ab0fc4c531&rfr_iscdi=true |