Low-Density Granulocytes Are Elevated in Mycobacterial Infection and Associated with the Severity of Tuberculosis
Tuberculosis remains a global health problem caused by infection with Mycobacterium tuberculosis. Numerous studies have established a close correlation between the development of tuberculosis and the roles of neutrophils. Recently, a distinct population of CD15+ granulocytes was found to be present...
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description | Tuberculosis remains a global health problem caused by infection with Mycobacterium tuberculosis. Numerous studies have established a close correlation between the development of tuberculosis and the roles of neutrophils. Recently, a distinct population of CD15+ granulocytes was found to be present in the peripheral blood mononuclear cell (PBMC) fraction in humans. This population of granulocytes, termed low-density granulocytes (LDGs), was reported to be elevated and associated with disease activity or severity in a number of different conditions including SLE, asthma and HIV infection. However, both the frequency and clinical significance of LDGs associated with tuberculosis are unclear. Here we determined LDG levels and made comparisons between subjects with active pulmonary tuberculosis (PTB) and healthy controls, between PTB patients with mild-to-moderate disease and patients with advanced disease, and among PTB patients following anti-tuberculous therapy of varying durations. The direct correlation between M. tuberculosis infection and LDG levels was confirmed by in vitro infection of whole peripheral blood and isolated granulocytes with mycobacteria. Our results demonstrated that PBMCs in PTB patients contained significantly elevated percentages of LDGs compared with control subjects. LDGs in tuberculosis expressed higher levels of activation markers compared to normal-density granulocytes (NDGs). M. tuberculosis induced the generation of LDGs in both whole blood and isolated NDGs from control subjects, which suggests that LDGs associated with M. tuberculosis infection are likely to originate from in situ activation. Furthermore, our results revealed that the frequency of LDGs is associated with the severity of tuberculosis. |
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Numerous studies have established a close correlation between the development of tuberculosis and the roles of neutrophils. Recently, a distinct population of CD15+ granulocytes was found to be present in the peripheral blood mononuclear cell (PBMC) fraction in humans. This population of granulocytes, termed low-density granulocytes (LDGs), was reported to be elevated and associated with disease activity or severity in a number of different conditions including SLE, asthma and HIV infection. However, both the frequency and clinical significance of LDGs associated with tuberculosis are unclear. Here we determined LDG levels and made comparisons between subjects with active pulmonary tuberculosis (PTB) and healthy controls, between PTB patients with mild-to-moderate disease and patients with advanced disease, and among PTB patients following anti-tuberculous therapy of varying durations. The direct correlation between M. tuberculosis infection and LDG levels was confirmed by in vitro infection of whole peripheral blood and isolated granulocytes with mycobacteria. Our results demonstrated that PBMCs in PTB patients contained significantly elevated percentages of LDGs compared with control subjects. LDGs in tuberculosis expressed higher levels of activation markers compared to normal-density granulocytes (NDGs). M. tuberculosis induced the generation of LDGs in both whole blood and isolated NDGs from control subjects, which suggests that LDGs associated with M. tuberculosis infection are likely to originate from in situ activation. Furthermore, our results revealed that the frequency of LDGs is associated with the severity of tuberculosis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0153567</identifier><identifier>PMID: 27073889</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Active control ; Adult ; Analysis ; Asthma ; Autoimmune diseases ; Biology and Life Sciences ; Blood ; Bronchoalveolar lavage ; Causes of ; Cell activation ; Correlation ; Correlation analysis ; Diagnosis ; Disease control ; Female ; Gene expression ; Global health ; Granulocytes ; Granulocytes - metabolism ; Granulocytes - pathology ; HIV ; Hospitals ; Human immunodeficiency virus ; Humans ; Infections ; Laboratories ; Leukocyte Count ; Leukocytes (granulocytic) ; Leukocytes (neutrophilic) ; Lewis X Antigen - metabolism ; Male ; Medical diagnosis ; Medicine and Health Sciences ; Middle Aged ; Mycobacterium tuberculosis ; Neutrophils ; Patients ; Peripheral blood mononuclear cells ; Population ; Population density ; Reactive Oxygen Species - metabolism ; Research and Analysis Methods ; Risk factors ; Severity of Illness Index ; Studies ; T cells ; Tuberculosis ; Tuberculosis, Pulmonary - pathology</subject><ispartof>PloS one, 2016-04, Vol.11 (4), p.e0153567-e0153567</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Deng 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 Deng et al 2016 Deng et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c776t-14ffffcfa425a0f67c606650c6a453b8000e4b22e518ca2d82f11141f6f1831d3</citedby><cites>FETCH-LOGICAL-c776t-14ffffcfa425a0f67c606650c6a453b8000e4b22e518ca2d82f11141f6f1831d3</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/PMC4830625/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830625/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2106,2932,23875,27933,27934,53800,53802</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27073889$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Scriba, Thomas Jens</contributor><creatorcontrib>Deng, Yating</creatorcontrib><creatorcontrib>Ye, Jianqing</creatorcontrib><creatorcontrib>Luo, Qing</creatorcontrib><creatorcontrib>Huang, Zhikun</creatorcontrib><creatorcontrib>Peng, Yiping</creatorcontrib><creatorcontrib>Xiong, Guoliang</creatorcontrib><creatorcontrib>Guo, Yang</creatorcontrib><creatorcontrib>Jiang, Hong</creatorcontrib><creatorcontrib>Li, Junming</creatorcontrib><title>Low-Density Granulocytes Are Elevated in Mycobacterial Infection and Associated with the Severity of Tuberculosis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Tuberculosis remains a global health problem caused by infection with Mycobacterium tuberculosis. 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Numerous studies have established a close correlation between the development of tuberculosis and the roles of neutrophils. Recently, a distinct population of CD15+ granulocytes was found to be present in the peripheral blood mononuclear cell (PBMC) fraction in humans. This population of granulocytes, termed low-density granulocytes (LDGs), was reported to be elevated and associated with disease activity or severity in a number of different conditions including SLE, asthma and HIV infection. However, both the frequency and clinical significance of LDGs associated with tuberculosis are unclear. Here we determined LDG levels and made comparisons between subjects with active pulmonary tuberculosis (PTB) and healthy controls, between PTB patients with mild-to-moderate disease and patients with advanced disease, and among PTB patients following anti-tuberculous therapy of varying durations. The direct correlation between M. tuberculosis infection and LDG levels was confirmed by in vitro infection of whole peripheral blood and isolated granulocytes with mycobacteria. Our results demonstrated that PBMCs in PTB patients contained significantly elevated percentages of LDGs compared with control subjects. LDGs in tuberculosis expressed higher levels of activation markers compared to normal-density granulocytes (NDGs). M. tuberculosis induced the generation of LDGs in both whole blood and isolated NDGs from control subjects, which suggests that LDGs associated with M. tuberculosis infection are likely to originate from in situ activation. Furthermore, our results revealed that the frequency of LDGs is associated with the severity of tuberculosis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27073889</pmid><doi>10.1371/journal.pone.0153567</doi><oa>free_for_read</oa></addata></record> |
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subjects | Active control Adult Analysis Asthma Autoimmune diseases Biology and Life Sciences Blood Bronchoalveolar lavage Causes of Cell activation Correlation Correlation analysis Diagnosis Disease control Female Gene expression Global health Granulocytes Granulocytes - metabolism Granulocytes - pathology HIV Hospitals Human immunodeficiency virus Humans Infections Laboratories Leukocyte Count Leukocytes (granulocytic) Leukocytes (neutrophilic) Lewis X Antigen - metabolism Male Medical diagnosis Medicine and Health Sciences Middle Aged Mycobacterium tuberculosis Neutrophils Patients Peripheral blood mononuclear cells Population Population density Reactive Oxygen Species - metabolism Research and Analysis Methods Risk factors Severity of Illness Index Studies T cells Tuberculosis Tuberculosis, Pulmonary - pathology |
title | Low-Density Granulocytes Are Elevated in Mycobacterial Infection and Associated with the Severity of Tuberculosis |
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