IL-10 blocks phagosome maturation in mycobacterium tuberculosis-infected human macrophages.

Abstract:

:Successful phagolysosomal maturation is an important innate immune response to intracellular infection. However, Mycobacterium tuberculosis (Mtb) can manipulate and inhibit this host response to ensure survival within its niche cell. We investigate the role of the anti-inflammatory cytokine IL-10 on Mtb-phagosome maturation. Blocking IL-10, which was secreted from Mtb-infected macrophages, allowed phagosome maturation to proceed. Macrophage cytokine gene expression profiles were not significantly altered by blocking IL-10 3 hours after infection with Mtb. We demonstrate that IL-10 can regulate this protective phenotype in phorbol myristate acetate (PMA)-treated THP-1 cells, monocyte-derived macrophages (MDMs), and human alveolar macrophages (AMs) infected with Mtb. The regulatory effect of endogenous IL-10 was evident in macrophages infected with virulent Mtb H37Rv, as well as in attenuated strains of mycobacteria. Unlike live Mtb, dead bacilli occupy a mature, acidic phagosome. However, the addition of IL-10 to cells infected with killed Mtb successfully inhibited the maturation of this compartment. Importantly, we demonstrate that the addition of IL-10 to MDMs results in enhanced mycobacterial survival and growth. Our results suggest that IL-10 exerts its effects on this early macrophage response in a partly signal transducer and activator of transcription 3 (STAT3)-dependent manner, and independent of mitogen activated protein kinase p38 (MAPKp38) and extracellular regulated kinase 1/2 (ERK1/2) activity. IL-10 is a feature of human tuberculous granuloma, and these new findings support the hypothesis that this cytokine can promote pathogen persistence by contributing to Mtb-phagosome maturation arrest in human macrophages.

authors

O'Leary S,O'Sullivan MP,Keane J

doi

10.1165/rcmb.2010-0319OC

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

172-80

issue

1

eissn

1044-1549

issn

1535-4989

pii

2010-0319OC

journal_volume

45

pub_type

杂志文章
  • Leukocyte elastase induces lung epithelial apoptosis via a PAR-1-, NF-kappaB-, and p53-dependent pathway.

    abstract::Leukocyte elastase induces apoptosis of lung epithelial cells via alterations in mitochondrial permeability, but the signaling pathways regulating this response remain uncertain. Here we investigated the involvement of proteinase-activated receptor-1 (PAR-1), the transcription factor NF-kappaB, and the protooncogene p...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2008-0157OC

    authors: Suzuki T,Yamashita C,Zemans RL,Briones N,Van Linden A,Downey GP

    更新日期:2009-12-01 00:00:00

  • Induction of vascular endothelial growth factor by platelet-activating factor and platelet-derived growth factor is downregulated by corticosteroids.

    abstract::Vascular endothelial growth factor (VEGF) is a potent peptide growth factor specific for vascular endothelial cells, which promotes neovascularization and increases vascular permeability in vivo. Enhanced microvascular permeability and edema are common characteristics of inflammatory and neoplastic disorders. Two proi...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.16.4.9115750

    authors: Nauck M,Roth M,Tamm M,Eickelberg O,Wieland H,Stulz P,Perruchoud AP

    更新日期:1997-04-01 00:00:00

  • Protein kinase C-epsilon regulates local calcium signaling in airway smooth muscle cells.

    abstract::Protein kinase C (PKC) is known to regulate ryanodine receptor (RyR)-mediated local Ca(2+) signaling (Ca(2+) spark) in airway and vascular smooth muscle cells (SMCs), but its specific molecular mechanisms and functions still remain elusive. In this study, we reveal that, in airway SMCs, specific PKCepsilon peptide inh...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2008-0323OC

    authors: Liu QH,Zheng YM,Korde AS,Li XQ,Ma J,Takeshima H,Wang YX

    更新日期:2009-06-01 00:00:00

  • Keratinocyte growth factor enhances maturation of fetal rat lung type II cells.

    abstract::Keratinocyte growth factor (KGF) or fibroblast growth factor (FGF)-7, a peptide produced by stromal cells and in particular by lung mesenchyme, has recently been shown to influence early lung morphogenesis and to be a mitogen for fetal and adult alveolar type II cells. Although contradictory findings have been reporte...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.20.3.3201

    authors: Chelly N,Mouhieddine-Gueddiche OB,Barlier-Mur AM,Chailley-Heu B,Bourbon JR

    更新日期:1999-03-01 00:00:00

  • Single-Nucleus RNA-Sequencing Profiling of Mouse Lung. Reduced Dissociation Bias and Improved Rare Cell-Type Detection Compared with Single-Cell RNA Sequencing.

    abstract::Single-cell RNA sequencing (scRNASeq) has advanced our understanding of lung biology, but its utility is limited by the need for fresh samples, loss of cell types by death or inadequate dissociation, and transcriptional stress responses induced during tissue digestion. Single-nucleus RNA sequencing (snRNASeq) has addr...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2020-0095MA

    authors: Koenitzer JR,Wu H,Atkinson JJ,Brody SL,Humphreys BD

    更新日期:2020-12-01 00:00:00

  • Age-related decrease in respiratory muscle mitochondrial function in rats.

    abstract::The purpose of this study was to elucidate the effects of aging on diaphragmatic mitochondrial function. Diaphragm mitochondria were prepared from specific pathogen-free rats aged 7 wk (n = 7), 35 wk (n = 7), and 55 wk (n = 7). The activities of various portions of the mitochondrial electron transport chain, i.e., com...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/6.1.88

    authors: Torii K,Sugiyama S,Takagi K,Satake T,Ozawa T

    更新日期:1992-01-01 00:00:00

  • Expression and regulation of a molecular marker, SPR1, in multistep bronchial carcinogenesis.

    abstract::A small proline-rich protein, SPR1, is overexpressed in squamous metaplasia of bronchial epithelium. We studied the expression and regulation of SPR1 in a series of human bronchial epithelial cell lines representing a model of multistep bronchial carcinogenesis. These cell lines included a primary culture of tracheobr...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.22.1.3637

    authors: Lau D,Xue L,Hu R,Liaw T,Wu R,Reddy S

    更新日期:2000-01-01 00:00:00

  • Integrative genetic analysis of allergic inflammation in the murine lung.

    abstract::Airway allergen exposure induces inflammation among individuals with atopy that is characterized by altered airway gene expression, elevated levels of T helper type 2 cytokines, mucus hypersecretion, and airflow obstruction. To identify the genetic determinants of the airway allergen response, we employed a systems ge...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2013-0501OC

    authors: Kelada SN,Carpenter DE,Aylor DL,Chines P,Rutledge H,Chesler EJ,Churchill GA,Pardo-Manuel de Villena F,Schwartz DA,Collins FS

    更新日期:2014-09-01 00:00:00

  • Isolation and partial characterization of pneumocin, a novel apical membrane surface glycoprotein marker of rat type II cells.

    abstract::Rat alveolar type II pneumocytes, in situ, label with Maclura pomifera agglutinin (MPA), a plant lectin that recognizes alpha-galactosyl oligosaccharide residues of glycoproteins and glycolipids. To study the glycoproteins recognized by the lectin, MPA lectin affinity chromatography was used to isolate a novel glycopr...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/4.6.479

    authors: Lwebuga-Mukasa JS

    更新日期:1991-06-01 00:00:00

  • Dry air-induced mucosal cell injury and bronchovascular leakage in canine peripheral airways.

    abstract::The purpose of this study was to examine the relationship between hyperpnea-induced mucosal injury, bronchovascular hyperpermeability, and airway reactivity. Hyperpnea-induced bronchoconstriction was assessed by measuring peripheral airway resistance (Rp) in anesthetized mechanically ventilated male mongrel dogs. Eith...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.11.6.7946400

    authors: Freed AN,Omori C,Schofield BH,Mitzner W

    更新日期:1994-12-01 00:00:00

  • Distribution of integrins alpha v beta 6 and alpha 9 beta 1 and their known ligands, fibronectin and tenascin, in human airways.

    abstract::We have previously identified two integrins, alpha 9 beta 1 and alpha v beta 6, from guinea pig airway epithelium. The extracellular matrix protein tenascin is a ligand for both of these receptors, and fibronectin is also a ligand for alpha v beta 6. In the present study, we used immunohistochemistry to examine the ex...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.12.5.7537970

    authors: Weinacker A,Ferrando R,Elliott M,Hogg J,Balmes J,Sheppard D

    更新日期:1995-05-01 00:00:00

  • Characterization of lung hyperresponsiveness, inflammation, and alveolar macrophage mediator production in allergy resistant and susceptible rats.

    abstract::To better understand asthma pathogenesis, we characterized airway responsiveness, lung inflammation, and mediator production of alveolar macrophages (AM) after allergen sensitization and challenge in two strains of rats showing different susceptibilities in developing airway allergic reactions. Airway responsiveness t...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.26.5.4737

    authors: Careau E,Sirois J,Bissonnette EY

    更新日期:2002-05-01 00:00:00

  • Induction of urokinase-type plasminogen activator receptor by IL-1 beta.

    abstract::Extensive tissue remodeling occurs in survivors of acute lung injury, leading to nearly normal histology and physiology in the majority of individuals, whereas others suffer significant impairment due to the development of pulmonary fibrosis. Alveolar epithelial cells play a central role in the repair process. They ar...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.16.6.9191470

    authors: Hasegawa T,Sorensen L,Dohi M,Rao NV,Hoidal JR,Marshall BC

    更新日期:1997-06-01 00:00:00

  • S-nitrosothiols inhibit cytokine-mediated induction of matrix metalloproteinase-9 in airway epithelial cells.

    abstract::Inflammatory lung diseases are associated with increased production of matrix metalloproteinase-9 (MMP-9) from infiltrating granulocytes or from the respiratory epithelium, and inappropriate expression and activation of MMP-9 may be associated with tissue injury and airway remodeling. Inflammatory conditions also resu...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2002-0039OC

    authors: Okamoto T,Valacchi G,Gohil K,Akaike T,van der Vliet A

    更新日期:2002-10-01 00:00:00

  • Lipoxin Signaling in Murine Lung Host Responses to Cryptococcus neoformans Infection.

    abstract::Lipoxins (LX) are proresolving mediators that augment host defense against bacterial infection. Here, we investigated roles for LX in lung clearance of the fungal pathogen Cryptococcus neoformans (Cne). After intranasal inoculation of 5,000 CFU Cne, C57BL/6 and C.B-17 mice exhibited strain-dependent differences in Cne...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2014-0102OC

    authors: Colby JK,Gott KM,Wilder JA,Levy BD

    更新日期:2016-01-01 00:00:00

  • A cystic fibrosis tracheal gland cell line, CF-KM4. Correction by adenovirus-mediated CFTR gene transfer.

    abstract::Human tracheal gland serous (HTGS) cells are now considered one principal pulmonary target for the gene therapy of cystic fibrosis (CF). We developed a CF tracheal gland serous cell line, CF-KM4, obtained by the transformation of primary cultures of CF tracheal gland serous cells homozygous for the DeltaF508 mutation ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.20.4.3341

    authors: Kammouni W,Moreau B,Becq F,Saleh A,Pavirani A,Figarella C,Merten MD

    更新日期:1999-04-01 00:00:00

  • Expression of granulocyte-macrophage colony-stimulating factor mRNA by inflammatory cells in the sarcoid lung.

    abstract::T lymphocytes and alveolar macrophages accumulating in the lower respiratory tract of patients with pulmonary sarcoidosis are known to be activated to produce several cytokines, presumably leading to granuloma formation within the lung. We hypothesized that these cells produce colony-stimulating factors (CSFs), which ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/3.3.245

    authors: Itoh A,Yamaguchi E,Kuzumaki N,Okazaki N,Furuya K,Abe S,Kawakami Y

    更新日期:1990-09-01 00:00:00

  • The effects of hyperoxic injury and antioxidant vitamins on death and proliferation of human small airway epithelial cells.

    abstract::Previously it was reported that hyperoxia induced death of the human lung adenocarcinoma cell line (A549 cells) by necrosis, not by apoptosis. This study examined proliferation and death of untransformed human small airway epithelial (SAE) cells in normoxia or hyperoxia in comparison with A549 cells. We tested the hyp...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.19.3.2862m

    authors: Jyonouchi H,Sun S,Abiru T,Chareancholvanich S,Ingbar DH

    更新日期:1998-09-01 00:00:00

  • Expression of immunoreactive and bioactive activin A protein in adult murine lung after bleomycin treatment.

    abstract::Activin A is a homodimeric protein structurally and functionally related to transforming growth factor beta (TGF-beta), and the expression of activin A is modulated by TGF-beta. Here, we demonstrate the expression of activin A in normal and bleomycin (BLM)-treated murine lungs. ICR mice were treated with BLM intraperi...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.13.1.7541220

    authors: Matsuse T,Fukuchi Y,Eto Y,Matsui H,Hosoi T,Oka T,Ohga E,Nagase T,Orimo H

    更新日期:1995-07-01 00:00:00

  • Sodium fluoride induces phosphoinositide hydrolysis, Ca2+ mobilization, and prostacyclin synthesis in cultured human endothelium: further evidence for regulation by a pertussis toxin-insensitive guanine nucleotide-binding protein.

    abstract::The role of guanine nucleotide-binding proteins in the induction of prostacyclin synthesis by stimulated endothelial cells is incompletely understood. We report that sodium fluoride (NaF), a potent activator of cellular guanine nucleotide-binding proteins, affected time- and concentration-dependent generation of prost...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/5.2.113

    authors: Garcia JG,Dominguez J,English D

    更新日期:1991-08-01 00:00:00

  • Airway epithelial epidermal growth factor receptor mediates hogbarn dust-induced cytokine release but not Ca2+ response.

    abstract::A subset of workers in swine confinement facilities develops chronic respiratory disease. An aqueous extract of dust from these facilities (hogbarn dust extract [HDE]) induces IL-6 and IL-8 release and several other responses in isolated airway epithelial cells. The cell membrane receptors by which HDE initiates these...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2010-0419OC

    authors: Dodmane PR,Schulte NA,Heires AJ,Band H,Romberger DJ,Toews ML

    更新日期:2011-10-01 00:00:00

  • The a"MAZE"ing world of lung-specific transgenic mice.

    abstract::The purpose of this review is to give a comprehensive overview of transgenic mouse lines suitable for studying gene function and cellular lineage relationships in lung development, homeostasis, injury, and repair. Many of the mouse strains reviewed in this Perspective have been widely shared within the lung research c...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章,评审

    doi:10.1165/rcmb.2011-0372PS

    authors: Rawlins EL,Perl AK

    更新日期:2012-03-01 00:00:00

  • Homologous human and murine antisense oligonucleotides targeting stat6. Functional effects on germline cepsilon transcript.

    abstract::Interleukin (IL)-4 and (IL)-13 induce immunoglobulin (Ig)E synthesis via activation of the transcription factor signal transducer and activator of transcription (Stat)6. The present study describes the identification and characterization of antisense oligonucleotides to Stat6 as an approach to interrupt IL-4 and IL-13...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.21.6.3709

    authors: Hill S,Herlaar E,Le Cardinal A,van Heeke G,Nicklin P

    更新日期:1999-12-01 00:00:00

  • Smoke extract impairs adenosine wound healing: implications of smoke-generated reactive oxygen species.

    abstract::Adenosine concentrations are elevated in the lungs of patients with asthma and chronic obstructive pulmonary disease, where it balances between tissue repair and excessive airway remodeling. We previously demonstrated that the activation of the adenosine A2A receptor promotes epithelial wound closure. However, the mec...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2011-0273OC

    authors: Allen-Gipson DS,Zimmerman MC,Zhang H,Castellanos G,O'Malley JK,Alvarez-Ramirez H,Kharbanda K,Sisson JH,Wyatt TA

    更新日期:2013-05-01 00:00:00

  • The Long Noncoding RNA LnRPT Is Regulated by PDGF-BB and Modulates the Proliferation of Pulmonary Artery Smooth Muscle Cells.

    abstract::Pulmonary artery hypertension (PAH) is a rare and fatal disorder that involves extensive remodeling of the pulmonary arteries mediated by hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Aberrant platelet-derived growth factor (PDGF) activity can lead to hyperproliferation of PASMCs; however, littl...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2017-0111OC

    authors: Chen J,Guo J,Cui X,Dai Y,Tang Z,Qu J,Raj JU,Hu Q,Gou D

    更新日期:2018-02-01 00:00:00

  • Hypersensitivity pneumonitis: whole Micropolyspora faeni or antigens thereof stimulate the release of proinflammatory cytokines from macrophages.

    abstract::Hypersensitivity pneumonitis (HP) is an allergic granulomatous interstitial lung disease resulting from a reaction of selected individuals to repeated inhalations of certain antigens. HP is characterized by chronic inflammation, and the development of the disease seems to be immunologically mediated. In farmer's lung,...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/5.2.198

    authors: Denis M,Cormier Y,Tardif J,Ghadirian E,Laviolette M

    更新日期:1991-08-01 00:00:00

  • Role of stretch on tight junction structure in alveolar epithelial cells.

    abstract::Previous studies have demonstrated that high tidal volumes can cause interstitial and alveolar edema, with degradation of pulmonary epithelial barrier integrity. Separate studies have shown that F-actin disruption and decreased intracellular ATP (ATP(i)) levels in the nonpulmonary epithelium can increase tight junctio...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.25.5.4486

    authors: Cavanaugh KJ Jr,Oswari J,Margulies SS

    更新日期:2001-11-01 00:00:00

  • Conditional recombination reveals distinct subsets of epithelial cells in trachea, bronchi, and alveoli.

    abstract::To identify relationships amongst tracheal and alveolar epithelial cells during lung development, we used conditional systems controlled by the rat CCSP and human SFTPC gene promoters to express Cre-recombinase in the developing mouse lung, thereby permanently labeling cells by expression of alkaline phosphatase or gr...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2005-0180OC

    authors: Perl AK,Wert SE,Loudy DE,Shan Z,Blair PA,Whitsett JA

    更新日期:2005-11-01 00:00:00

  • Tobramycin and FDA-approved iron chelators eliminate Pseudomonas aeruginosa biofilms on cystic fibrosis cells.

    abstract::The ability of Pseudomonas aeruginosa to form antibiotic-resistant biofilms is thought to account for the inability of current therapies to resolve bacterial infections in the lungs of patients with cystic fibrosis (CF). We recently described a system in which highly antibiotic-resistant P. aeruginosa biofilms grow on...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2008-0299OC

    authors: Moreau-Marquis S,O'Toole GA,Stanton BA

    更新日期:2009-09-01 00:00:00

  • MD-2-dependent pulmonary immune responses to inhaled lipooligosaccharides: effect of acylation state.

    abstract::Endotoxins represent one of the most potent classes of microbial immunoactive components that can cause pulmonary inflammation. The aim of this study was to compare the inflammatory potency of two types of Neisseria meningitidis endotoxins (lipooligosaccharides) in lungs: wild type (hexaacylated, LOS(wt)) and mutant t...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0418OC

    authors: Hadina S,Weiss JP,McCray PB Jr,Kulhankova K,Thorne PS

    更新日期:2008-06-01 00:00:00