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The Defect in Autophagy Induction by Clinical Isolates of Mycobacterium Tuberculosis Is Correlated with Poor Tuberculosis Outcomes
Tuberculosis (TB) represents a major global health problem. The prognosis of clinically active tuberculosis depends on the complex interactions between Mycobacterium tuberculosis (Mtb) and its host. In recent years, autophagy receives particular attention for its role in host defense against intrace...
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| Published in: | PloS one 2016-01, Vol.11 (1), p.e0147810-e0147810 |
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| creator | Li, Furong Gao, Bo Xu, Wei Chen, Ling Xiong, Sidong |
| description | Tuberculosis (TB) represents a major global health problem. The prognosis of clinically active tuberculosis depends on the complex interactions between Mycobacterium tuberculosis (Mtb) and its host. In recent years, autophagy receives particular attention for its role in host defense against intracellular pathogens, including Mtb. In present study, we aim to investigate the relationship of autophagy induction by clinical isolates of Mtb with the clinical outcomes in patients with TB.
We collected 185 clinical isolates of Mtb, and determined the effect of these Mtb isolates on autophagy induction in macrophages. It was found that most of clinical isolates of Mtb were able to induce autophagosome formation in macrophages, however, the autophagy-inducing ability varied significantly among different isolates. Of importance, our results revealed that patients infected by Mtb with poor autophagy-inducing ability displayed more severe radiographic extent of disease (p |
| doi_str_mv | 10.1371/journal.pone.0147810 |
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We collected 185 clinical isolates of Mtb, and determined the effect of these Mtb isolates on autophagy induction in macrophages. It was found that most of clinical isolates of Mtb were able to induce autophagosome formation in macrophages, however, the autophagy-inducing ability varied significantly among different isolates. Of importance, our results revealed that patients infected by Mtb with poor autophagy-inducing ability displayed more severe radiographic extent of disease (p<0.001), and were more likely to have unfavorable treatment outcomes (p<0.001). No significant association was observed between the extent of Mtb-induced autophagy with some socio-demographic characteristics (such as gender, age and tobacco consumption), and some laboratory tests (such as hemoglobin, leukocyte count and erythrocyte sedimentation rate). Furthermore, results from logistic regression analysis demonstrated that the defect in autophagy induction by clinical isolates of Mtb was an independent risk factor for far-advanced radiographic disease (aOR 4.710 [1.93-11.50]) and unfavorable treatment outcomes (aOR 8.309 [2.22-28.97]) in TB.
These data indicated that the defect in autophagy induction by Mtb isolates increased the risk of poor clinical outcomes in TB patients, and detection of clinical isolates-induced autophagosome formation might help evaluate the TB outcomes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0147810</identifier><identifier>PMID: 26815035</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Animals ; Antibiotics ; Antitubercular Agents ; Autophagy ; Autophagy (Cytology) ; Biology and Life Sciences ; Cell death ; Cell Line ; Clinical isolates ; Demographics ; Drug resistance ; Erythrocyte sedimentation rate ; Erythrocytes ; Female ; Genetic aspects ; Genetic diversity ; Global health ; Health risks ; Hemoglobin ; Host-Pathogen Interactions ; Humans ; Immunology ; Infections ; Laboratories ; Laboratory tests ; Leukocytes ; Macrophages ; Macrophages - microbiology ; Macrophages - pathology ; Male ; Medicine and Health Sciences ; Mice ; Middle Aged ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - isolation & purification ; Mycobacterium tuberculosis - physiology ; Pathogenesis ; Patient outcomes ; Patients ; Phagocytosis ; Physical Sciences ; Physiological aspects ; Prognosis ; Regression analysis ; Research and Analysis Methods ; Respiratory diseases ; Risk factors ; Studies ; Tobacco ; Treatment Outcome ; Tuberculosis ; Tuberculosis - diagnosis ; Tuberculosis - epidemiology ; Tuberculosis - physiopathology ; Tuberculosis - therapy</subject><ispartof>PloS one, 2016-01, Vol.11 (1), p.e0147810-e0147810</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Li et al 2016 Li et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-2d1df4494a032317d8a62ba48cad5f94dfc3efb30da66fc52cf60439feada3953</citedby><cites>FETCH-LOGICAL-c692t-2d1df4494a032317d8a62ba48cad5f94dfc3efb30da66fc52cf60439feada3953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1760838846/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1760838846?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,25734,27905,27906,36993,36994,44571,53772,53774,74875</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26815035$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Delogu, Giovanni</contributor><creatorcontrib>Li, Furong</creatorcontrib><creatorcontrib>Gao, Bo</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Chen, Ling</creatorcontrib><creatorcontrib>Xiong, Sidong</creatorcontrib><title>The Defect in Autophagy Induction by Clinical Isolates of Mycobacterium Tuberculosis Is Correlated with Poor Tuberculosis Outcomes</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Tuberculosis (TB) represents a major global health problem. The prognosis of clinically active tuberculosis depends on the complex interactions between Mycobacterium tuberculosis (Mtb) and its host. In recent years, autophagy receives particular attention for its role in host defense against intracellular pathogens, including Mtb. In present study, we aim to investigate the relationship of autophagy induction by clinical isolates of Mtb with the clinical outcomes in patients with TB.
We collected 185 clinical isolates of Mtb, and determined the effect of these Mtb isolates on autophagy induction in macrophages. It was found that most of clinical isolates of Mtb were able to induce autophagosome formation in macrophages, however, the autophagy-inducing ability varied significantly among different isolates. Of importance, our results revealed that patients infected by Mtb with poor autophagy-inducing ability displayed more severe radiographic extent of disease (p<0.001), and were more likely to have unfavorable treatment outcomes (p<0.001). No significant association was observed between the extent of Mtb-induced autophagy with some socio-demographic characteristics (such as gender, age and tobacco consumption), and some laboratory tests (such as hemoglobin, leukocyte count and erythrocyte sedimentation rate). Furthermore, results from logistic regression analysis demonstrated that the defect in autophagy induction by clinical isolates of Mtb was an independent risk factor for far-advanced radiographic disease (aOR 4.710 [1.93-11.50]) and unfavorable treatment outcomes (aOR 8.309 [2.22-28.97]) in TB.
These data indicated that the defect in autophagy induction by Mtb isolates increased the risk of poor clinical outcomes in TB patients, and detection of clinical isolates-induced autophagosome formation might help evaluate the TB outcomes.</description><subject>Adult</subject><subject>Animals</subject><subject>Antibiotics</subject><subject>Antitubercular Agents</subject><subject>Autophagy</subject><subject>Autophagy (Cytology)</subject><subject>Biology and Life Sciences</subject><subject>Cell death</subject><subject>Cell Line</subject><subject>Clinical isolates</subject><subject>Demographics</subject><subject>Drug resistance</subject><subject>Erythrocyte sedimentation rate</subject><subject>Erythrocytes</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Global health</subject><subject>Health risks</subject><subject>Hemoglobin</subject><subject>Host-Pathogen Interactions</subject><subject>Humans</subject><subject>Immunology</subject><subject>Infections</subject><subject>Laboratories</subject><subject>Laboratory tests</subject><subject>Leukocytes</subject><subject>Macrophages</subject><subject>Macrophages - microbiology</subject><subject>Macrophages - pathology</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - isolation & purification</subject><subject>Mycobacterium tuberculosis - physiology</subject><subject>Pathogenesis</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Phagocytosis</subject><subject>Physical Sciences</subject><subject>Physiological aspects</subject><subject>Prognosis</subject><subject>Regression analysis</subject><subject>Research and Analysis Methods</subject><subject>Respiratory diseases</subject><subject>Risk factors</subject><subject>Studies</subject><subject>Tobacco</subject><subject>Treatment Outcome</subject><subject>Tuberculosis</subject><subject>Tuberculosis - diagnosis</subject><subject>Tuberculosis - epidemiology</subject><subject>Tuberculosis - physiopathology</subject><subject>Tuberculosis - 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microbiology</topic><topic>Macrophages - pathology</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Middle Aged</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - isolation & purification</topic><topic>Mycobacterium tuberculosis - physiology</topic><topic>Pathogenesis</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>Phagocytosis</topic><topic>Physical Sciences</topic><topic>Physiological aspects</topic><topic>Prognosis</topic><topic>Regression analysis</topic><topic>Research and Analysis Methods</topic><topic>Respiratory diseases</topic><topic>Risk factors</topic><topic>Studies</topic><topic>Tobacco</topic><topic>Treatment Outcome</topic><topic>Tuberculosis</topic><topic>Tuberculosis - diagnosis</topic><topic>Tuberculosis - epidemiology</topic><topic>Tuberculosis - physiopathology</topic><topic>Tuberculosis - therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Furong</creatorcontrib><creatorcontrib>Gao, Bo</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Chen, Ling</creatorcontrib><creatorcontrib>Xiong, Sidong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Databases</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Furong</au><au>Gao, Bo</au><au>Xu, Wei</au><au>Chen, Ling</au><au>Xiong, Sidong</au><au>Delogu, Giovanni</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Defect in Autophagy Induction by Clinical Isolates of Mycobacterium Tuberculosis Is Correlated with Poor Tuberculosis Outcomes</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-01-27</date><risdate>2016</risdate><volume>11</volume><issue>1</issue><spage>e0147810</spage><epage>e0147810</epage><pages>e0147810-e0147810</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Tuberculosis (TB) represents a major global health problem. The prognosis of clinically active tuberculosis depends on the complex interactions between Mycobacterium tuberculosis (Mtb) and its host. In recent years, autophagy receives particular attention for its role in host defense against intracellular pathogens, including Mtb. In present study, we aim to investigate the relationship of autophagy induction by clinical isolates of Mtb with the clinical outcomes in patients with TB.
We collected 185 clinical isolates of Mtb, and determined the effect of these Mtb isolates on autophagy induction in macrophages. It was found that most of clinical isolates of Mtb were able to induce autophagosome formation in macrophages, however, the autophagy-inducing ability varied significantly among different isolates. Of importance, our results revealed that patients infected by Mtb with poor autophagy-inducing ability displayed more severe radiographic extent of disease (p<0.001), and were more likely to have unfavorable treatment outcomes (p<0.001). No significant association was observed between the extent of Mtb-induced autophagy with some socio-demographic characteristics (such as gender, age and tobacco consumption), and some laboratory tests (such as hemoglobin, leukocyte count and erythrocyte sedimentation rate). Furthermore, results from logistic regression analysis demonstrated that the defect in autophagy induction by clinical isolates of Mtb was an independent risk factor for far-advanced radiographic disease (aOR 4.710 [1.93-11.50]) and unfavorable treatment outcomes (aOR 8.309 [2.22-28.97]) in TB.
These data indicated that the defect in autophagy induction by Mtb isolates increased the risk of poor clinical outcomes in TB patients, and detection of clinical isolates-induced autophagosome formation might help evaluate the TB outcomes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26815035</pmid><doi>10.1371/journal.pone.0147810</doi><tpages>e0147810</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Animals Antibiotics Antitubercular Agents Autophagy Autophagy (Cytology) Biology and Life Sciences Cell death Cell Line Clinical isolates Demographics Drug resistance Erythrocyte sedimentation rate Erythrocytes Female Genetic aspects Genetic diversity Global health Health risks Hemoglobin Host-Pathogen Interactions Humans Immunology Infections Laboratories Laboratory tests Leukocytes Macrophages Macrophages - microbiology Macrophages - pathology Male Medicine and Health Sciences Mice Middle Aged Mycobacterium tuberculosis Mycobacterium tuberculosis - isolation & purification Mycobacterium tuberculosis - physiology Pathogenesis Patient outcomes Patients Phagocytosis Physical Sciences Physiological aspects Prognosis Regression analysis Research and Analysis Methods Respiratory diseases Risk factors Studies Tobacco Treatment Outcome Tuberculosis Tuberculosis - diagnosis Tuberculosis - epidemiology Tuberculosis - physiopathology Tuberculosis - therapy |
| title | The Defect in Autophagy Induction by Clinical Isolates of Mycobacterium Tuberculosis Is Correlated with Poor Tuberculosis Outcomes |
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