Azurophil granule proteins constitute the major mycobactericidal proteins in human neutrophils and enhance the killing of mycobacteria in macrophages
Pathogenic mycobacteria reside in, and are in turn controlled by, macrophages. However, emerging data suggest that neutrophils also play a critical role in innate immunity to tuberculosis, presumably by their different antibacterial granule proteins. In this study, we purified neutrophil azurophil a...
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| Veröffentlicht in: | PloS one 2012-12, Vol.7 (12), p.e50345-e50345 |
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| creator | Jena, Prajna Mohanty, Soumitra Mohanty, Tirthankar Kallert, Stephanie Morgelin, Matthias Lindstrøm, Thomas Borregaard, Niels Stenger, Steffen Sonawane, Avinash Sørensen, Ole E |
| description | Pathogenic mycobacteria reside in, and are in turn controlled by, macrophages. However, emerging data suggest that neutrophils also play a critical role in innate immunity to tuberculosis, presumably by their different antibacterial granule proteins. In this study, we purified neutrophil azurophil and specific granules and systematically analyzed the antimycobacterial activity of some purified azurophil and specific granule proteins against M. smegmatis, M. bovis-BCG and M. tuberculosis H37Rv. Using gel overlay and colony forming unit assays we showed that the defensin-depleted azurophil granule proteins (AZP) were more active against mycobacteria compared to other granule proteins and cytosolic proteins. The proteins showing antimycobacterial activity were identified by MALDI-TOF mass spectrometry. Electron microscopic studies demonstrate that the AZP disintegrate bacterial cell membrane resulting in killing of mycobacteria. Exogenous addition of AZP to murine macrophage RAW 264.7, THP-1 and peripheral blood monocyte-derived macrophages significantly reduced the intracellular survival of mycobacteria without exhibiting cytotoxic activity on macrophages. Immunofluorescence studies showed that macrophages actively endocytose neutrophil granular proteins. Treatment with AZP resulted in increase in co-localization of BCG containing phagosomes with lysosomes but not in increase of autophagy. These data demonstrate that neutrophil azurophil proteins may play an important role in controlling intracellular survival of mycobacteria in macrophages. |
| doi_str_mv | 10.1371/journal.pone.0050345 |
| format | Article |
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However, emerging data suggest that neutrophils also play a critical role in innate immunity to tuberculosis, presumably by their different antibacterial granule proteins. In this study, we purified neutrophil azurophil and specific granules and systematically analyzed the antimycobacterial activity of some purified azurophil and specific granule proteins against M. smegmatis, M. bovis-BCG and M. tuberculosis H37Rv. Using gel overlay and colony forming unit assays we showed that the defensin-depleted azurophil granule proteins (AZP) were more active against mycobacteria compared to other granule proteins and cytosolic proteins. The proteins showing antimycobacterial activity were identified by MALDI-TOF mass spectrometry. Electron microscopic studies demonstrate that the AZP disintegrate bacterial cell membrane resulting in killing of mycobacteria. Exogenous addition of AZP to murine macrophage RAW 264.7, THP-1 and peripheral blood monocyte-derived macrophages significantly reduced the intracellular survival of mycobacteria without exhibiting cytotoxic activity on macrophages. Immunofluorescence studies showed that macrophages actively endocytose neutrophil granular proteins. Treatment with AZP resulted in increase in co-localization of BCG containing phagosomes with lysosomes but not in increase of autophagy. These data demonstrate that neutrophil azurophil proteins may play an important role in controlling intracellular survival of mycobacteria in macrophages.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0050345</identifier><identifier>PMID: 23251364</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Antibacterial agents ; Antimicrobial agents ; Autophagy ; Azurophil ; Bacillus Calmette-Guerin vaccine ; Bacteria ; BCG ; Biology ; Biotechnology ; Cell survival ; Clinical Medicine ; Comparative analysis ; Cytoplasmic Granules - metabolism ; Cytotoxicity ; Gene expression ; Granular materials ; Granulocytes ; Humans ; Immunity ; Immunofluorescence ; Infections ; Infectious Medicine ; Infektionsmedicin ; Innate immunity ; Intracellular ; Killing ; Kinases ; Klinisk medicin ; Leukocytes (neutrophilic) ; Localization ; Lysosomes ; Lysosomes - immunology ; Lysosomes - metabolism ; Lysosomes - microbiology ; Macrophages ; Macrophages - immunology ; Macrophages - metabolism ; Macrophages - microbiology ; Mass spectrometry ; Mass spectroscopy ; Medical and Health Sciences ; Medical research ; Medicin och hälsovetenskap ; Medicine ; Monocytes ; Mycobacterium ; Mycobacterium bovis ; Mycobacterium tuberculosis ; Neutrophils ; Neutrophils - immunology ; Neutrophils - metabolism ; Neutrophils - microbiology ; Peripheral blood ; Phagocytosis ; Phagosomes ; Phagosomes - immunology ; Phagosomes - metabolism ; Phagosomes - microbiology ; Proteins ; Studies ; Survival ; Tuberculosis</subject><ispartof>PloS one, 2012-12, Vol.7 (12), p.e50345-e50345</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Jena et al. 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However, emerging data suggest that neutrophils also play a critical role in innate immunity to tuberculosis, presumably by their different antibacterial granule proteins. In this study, we purified neutrophil azurophil and specific granules and systematically analyzed the antimycobacterial activity of some purified azurophil and specific granule proteins against M. smegmatis, M. bovis-BCG and M. tuberculosis H37Rv. Using gel overlay and colony forming unit assays we showed that the defensin-depleted azurophil granule proteins (AZP) were more active against mycobacteria compared to other granule proteins and cytosolic proteins. The proteins showing antimycobacterial activity were identified by MALDI-TOF mass spectrometry. Electron microscopic studies demonstrate that the AZP disintegrate bacterial cell membrane resulting in killing of mycobacteria. 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These data demonstrate that neutrophil azurophil proteins may play an important role in controlling intracellular survival of mycobacteria in macrophages.</description><subject>Antibacterial agents</subject><subject>Antimicrobial agents</subject><subject>Autophagy</subject><subject>Azurophil</subject><subject>Bacillus Calmette-Guerin vaccine</subject><subject>Bacteria</subject><subject>BCG</subject><subject>Biology</subject><subject>Biotechnology</subject><subject>Cell survival</subject><subject>Clinical Medicine</subject><subject>Comparative analysis</subject><subject>Cytoplasmic Granules - metabolism</subject><subject>Cytotoxicity</subject><subject>Gene expression</subject><subject>Granular materials</subject><subject>Granulocytes</subject><subject>Humans</subject><subject>Immunity</subject><subject>Immunofluorescence</subject><subject>Infections</subject><subject>Infectious Medicine</subject><subject>Infektionsmedicin</subject><subject>Innate 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One</addtitle><date>2012-12-14</date><risdate>2012</risdate><volume>7</volume><issue>12</issue><spage>e50345</spage><epage>e50345</epage><pages>e50345-e50345</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Pathogenic mycobacteria reside in, and are in turn controlled by, macrophages. However, emerging data suggest that neutrophils also play a critical role in innate immunity to tuberculosis, presumably by their different antibacterial granule proteins. In this study, we purified neutrophil azurophil and specific granules and systematically analyzed the antimycobacterial activity of some purified azurophil and specific granule proteins against M. smegmatis, M. bovis-BCG and M. tuberculosis H37Rv. Using gel overlay and colony forming unit assays we showed that the defensin-depleted azurophil granule proteins (AZP) were more active against mycobacteria compared to other granule proteins and cytosolic proteins. The proteins showing antimycobacterial activity were identified by MALDI-TOF mass spectrometry. Electron microscopic studies demonstrate that the AZP disintegrate bacterial cell membrane resulting in killing of mycobacteria. Exogenous addition of AZP to murine macrophage RAW 264.7, THP-1 and peripheral blood monocyte-derived macrophages significantly reduced the intracellular survival of mycobacteria without exhibiting cytotoxic activity on macrophages. Immunofluorescence studies showed that macrophages actively endocytose neutrophil granular proteins. Treatment with AZP resulted in increase in co-localization of BCG containing phagosomes with lysosomes but not in increase of autophagy. These data demonstrate that neutrophil azurophil proteins may play an important role in controlling intracellular survival of mycobacteria in macrophages.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23251364</pmid><doi>10.1371/journal.pone.0050345</doi><tpages>e50345</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-12, Vol.7 (12), p.e50345-e50345 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1327124346 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; SWEPUB Freely available online; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Antibacterial agents Antimicrobial agents Autophagy Azurophil Bacillus Calmette-Guerin vaccine Bacteria BCG Biology Biotechnology Cell survival Clinical Medicine Comparative analysis Cytoplasmic Granules - metabolism Cytotoxicity Gene expression Granular materials Granulocytes Humans Immunity Immunofluorescence Infections Infectious Medicine Infektionsmedicin Innate immunity Intracellular Killing Kinases Klinisk medicin Leukocytes (neutrophilic) Localization Lysosomes Lysosomes - immunology Lysosomes - metabolism Lysosomes - microbiology Macrophages Macrophages - immunology Macrophages - metabolism Macrophages - microbiology Mass spectrometry Mass spectroscopy Medical and Health Sciences Medical research Medicin och hälsovetenskap Medicine Monocytes Mycobacterium Mycobacterium bovis Mycobacterium tuberculosis Neutrophils Neutrophils - immunology Neutrophils - metabolism Neutrophils - microbiology Peripheral blood Phagocytosis Phagosomes Phagosomes - immunology Phagosomes - metabolism Phagosomes - microbiology Proteins Studies Survival Tuberculosis |
| title | Azurophil granule proteins constitute the major mycobactericidal proteins in human neutrophils and enhance the killing of mycobacteria in macrophages |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T16%3A26%3A35IST&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=Azurophil%20granule%20proteins%20constitute%20the%20major%20mycobactericidal%20proteins%20in%20human%20neutrophils%20and%20enhance%20the%20killing%20of%20mycobacteria%20in%20macrophages&rft.jtitle=PloS%20one&rft.au=Jena,%20Prajna&rft.date=2012-12-14&rft.volume=7&rft.issue=12&rft.spage=e50345&rft.epage=e50345&rft.pages=e50345-e50345&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0050345&rft_dat=%3Cgale_plos_%3EA477083571%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=1327124346&rft_id=info:pmid/23251364&rft_galeid=A477083571&rft_doaj_id=oai_doaj_org_article_0230893362ac4e3f9b7578d0c4bba2e2&rfr_iscdi=true |