Database : MEDLINE
Search on : Macrophage and Activation [Words]
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[PMID]: 29524539
[Au] Autor:Lejal N; Truchet S; Bechor E; Bouguyon E; Khedkar V; Bertho N; Vidic J; Adenot P; Solier S; Pick E; Slama-Schwok A
[Ad] Address:Paris Saclay University, U892 INRA, Jouy en Josas, France.
[Ti] Title:Turning off NADPH oxidase-2 by impeding p67 activation in infected mouse macrophages reduced viral entry and inflammation.
[So] Source:Biochim Biophys Acta;, 2018 Mar 07.
[Is] ISSN:0006-3002
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND: Targeting cells of the host immune system is a promising approach to fight against Influenza A virus (IAV) infection. Macrophage cells use the NADPH oxidase-2 (NOX2) enzymatic complex as a first line of defense against pathogens by generating superoxide ions O and releasing H O . Herein, we investigated whether targeting membrane -embedded NOX2 decreased IAV entry via raft domains and reduced inflammation in infected macrophages. METHODS: Confocal microscopy and western blots monitored levels of the viral nucleoprotein NP and p67 , NOX2 activator subunit, Elisa assays quantified TNF-α levels in LPS or IAV-activated mouse or porcine alveolar macrophages pretreated with a fluorescent NOX inhibitor, called nanoshutter NS1. RESULTS: IAV infection in macrophages promoted p67 translocation to the membrane, rafts clustering and activation of the NOX2 complex at early times. Disrupting rafts reduced intracellular viral NP. NS1 markedly reduced raft clustering and viral entry by binding to the C-terminal of NOX2 also characterized in vitro. NS1 decrease of TNF-α release depended on the cell type. CONCLUSION: NOX2 participated in IAV entry and raft-mediated endocytosis. NOX2 inhibition by NS1 reduced viral entry. NS1 competition with p67 for NOX2 binding shown by in silico models and cell-free assays was in agreement with NS1 inhibiting p67 translocation to membrane-embedded NOX2 in mouse and porcine macrophages. GENERAL SIGNIFICANCE: We introduce NS1 as a compound targeting NOX2, a critical enzyme controlling viral levels and inflammation in macrophages and discuss the therapeutic relevance of targeting the C-terminal of NADPH oxidases by probes like NS1 in viral infections.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  2 / 84590 MEDLINE  
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[PMID]: 29510721
[Au] Autor:Gill AJ; Garza R; Ambegaokar SS; Gelman BB; Kolson DL
[Ad] Address:Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 415 Curie Boulevard, 280C Clinical Research Building, Philadelphia, PA, 19104, USA.
[Ti] Title:Heme oxygenase-1 promoter region (GT)n polymorphism associates with increased neuroimmune activation and risk for encephalitis in HIV infection.
[So] Source:J Neuroinflammation;15(1):70, 2018 Mar 06.
[Is] ISSN:1742-2094
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Heme oxygenase-1 (HO-1) is a critical cytoprotective enzyme that limits oxidative stress, inflammation, and cellular injury within the central nervous system (CNS) and other tissues. We previously demonstrated that HO-1 protein expression is decreased within the brains of HIV+ subjects and that this HO-1 reduction correlates with CNS immune activation and neurocognitive dysfunction. To define a potential CNS protective role for HO-1 against HIV, we analyzed a well-characterized HIV autopsy cohort for two common HO-1 promoter region polymorphisms that are implicated in regulating HO-1 promoter transcriptional activity, a (GT)n dinucleotide repeat polymorphism and a single nucleotide polymorphism (A(-413)T). Shorter HO-1 (GT)n repeats and the 'A' SNP allele associate with higher HO-1 promoter activity. METHODS: Brain dorsolateral prefrontal cortex tissue samples from an autopsy cohort of HIV-, HIV+, and HIV encephalitis (HIVE) subjects (n = 554) were analyzed as follows: HO-1 (GT)n polymorphism allele lengths were determined by PCR and capillary electrophoresis, A(-413)T SNP alleles were determined by PCR with allele specific probes, and RNA expression of selected neuroimmune markers was analyzed by quantitative PCR. RESULTS: HIV+ subjects with shorter HO-1 (GT)n alleles had a significantly lower risk of HIVE; however, shorter HO-1 (GT)n alleles did not correlate with CNS or peripheral viral loads. In HIV+ subjects without HIVE, shorter HO-1 (GT)n alleles associated significantly with lower expression of brain type I interferon response markers (MX1, ISG15, and IRF1) and T-lymphocyte activation markers (CD38 and GZMB). No significant correlations were found between the HO-1 (GT)n repeat length and brain expression of macrophage markers (CD163, CD68), endothelial markers (PECAM1, VWF), the T-lymphocyte marker CD8A, or the B-lymphocyte maker CD19. Finally, we found no significant associations between the A(-413)T SNP and HIVE diagnosis, HIV viral loads, or any neuroimmune markers. CONCLUSION: Our data suggest that an individual's HO-1 promoter region (GT)n polymorphism allele repeat length exerts unique modifying risk effects on HIV-induced CNS neuroinflammation and associated neuropathogenesis. Shorter HO-1 (GT)n alleles increase HO-1 promoter activity, which could provide neuroprotection through decreased neuroimmune activation. Therapeutic strategies that induce HO-1 expression could decrease HIV-associated CNS neuroinflammation and decrease the risk for development of HIV neurological disease.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Data-Review
[do] DOI:10.1186/s12974-018-1102-z

  3 / 84590 MEDLINE  
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[PMID]: 29269377
[Au] Autor:Duperret EK; Trautz A; Ammons D; Perales-Puchalt A; Wise MC; Yan J; Reed C; Weiner DB
[Ad] Address:Vaccine Center, The Wistar Institute, Philadelphia, Pennsylvania.
[Ti] Title:Alteration of the Tumor Stroma Using a Consensus DNA Vaccine Targeting Fibroblast Activation Protein (FAP) Synergizes with Antitumor Vaccine Therapy in Mice.
[So] Source:Clin Cancer Res;24(5):1190-1201, 2018 Mar 01.
[Is] ISSN:1078-0432
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts and is an interesting target for cancer immune therapy, with prior studies indicating a potential to affect the tumor stroma. Our aim was to extend this earlier work through the development of a novel FAP immunogen with improved capacity to break tolerance for use in combination with tumor antigen vaccines. We used a synthetic consensus (SynCon) sequence approach to provide MHC class II help to support breaking of tolerance. We evaluated immune responses and antitumor activity of this novel FAP vaccine in preclinical studies, and correlated these findings to patient data. This SynCon FAP DNA vaccine was capable of breaking tolerance and inducing both CD8 and CD4 immune responses. In genetically diverse, outbred mice, the SynCon FAP DNA vaccine was superior at breaking tolerance compared with a native mouse FAP immunogen. In several tumor models, the SynCon FAP DNA vaccine synergized with other tumor antigen-specific DNA vaccines to enhance antitumor immunity. Evaluation of the tumor microenvironment showed increased CD8 T-cell infiltration and a decreased macrophage infiltration driven by FAP immunization. We extended this to patient data from The Cancer Genome Atlas, where we find high FAP expression correlates with high macrophage and low CD8 T-cell infiltration. These results suggest that immune therapy targeting tumor antigens in combination with a microconsensus FAP vaccine provides two-fisted punch-inducing responses that target both the tumor microenvironment and tumor cells directly. .
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Data-Review
[do] DOI:10.1158/1078-0432.CCR-17-2033

  4 / 84590 MEDLINE  
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[PMID]: 29249750
[Au] Autor:Sugihara H; Miyaji K; Yamanouchi K; Matsuwaki T; Nishihara M
[Ad] Address:Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
[Ti] Title:Progranulin deficiency leads to prolonged persistence of macrophages, accompanied with myofiber hypertrophy in regenerating muscle.
[So] Source:J Vet Med Sci;80(2):346-353, 2018 Mar 02.
[Is] ISSN:1347-7439
[Cp] Country of publication:Japan
[La] Language:eng
[Ab] Abstract:Skeletal muscle has an ability to regenerate in response to injury due to the presence of satellite cells. Injury in skeletal muscle causes infiltration of pro-inflammatory macrophages (M1 macrophages) to remove necrotic myofibers, followed by their differentiation into anti-inflammatory macrophages (M2 macrophages) to terminate the inflammation. Since both M1 and M2 macrophages play important roles, coordinated regulation of their kinetics is important to complete muscle regeneration successfully. Progranulin (PGRN) is a pluripotent growth factor, having a protective role against the inflamed tissue. In the central nervous system, PGRN regulates inflammation by inhibiting the activation of microglia. Here we used muscle injury model of PGRN-knockout (PGRN-KO) mice to elucidate whether it has a role in the kinetics of macrophages during muscle regeneration. We found the prolonged persistence of macrophages at the late phase of regeneration in PGRN-KO mice, and these macrophages were suggested to be M2 macrophages since this was accompanied with an increased CD206 expression. We also observed muscle hypertrophy in PGRN-KO mice at the late stage of muscle regeneration. Since M2 macrophages are known to have a role in maturation of myofibers, this muscle hypertrophy may be due to the presence of increased number of M2 macrophages. Our results suggest that PGRN plays a role in the regulation of kinetics of macrophages for the systemic progress of muscle regeneration.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Process
[do] DOI:10.1292/jvms.17-0638

  5 / 84590 MEDLINE  
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[PMID]: 28463821
[Au] Autor:Hoyt LR; Randall MJ; Ather JL; DePuccio DP; Landry CC; Qian X; Janssen-Heininger YM; van der Vliet A; Dixon AE; Amiel E; Poynter ME
[Ad] Address:Vermont Lung Center, University of Vermont, Burlington, VT 05405, USA; Division of Pulmonary Disease and Critical Care, Department of Medicine, University of Vermont, Burlington, VT 05405, USA.
[Ti] Title:Mitochondrial ROS induced by chronic ethanol exposure promote hyper-activation of the NLRP3 inflammasome.
[So] Source:Redox Biol;12:883-896, 2017 Aug.
[Is] ISSN:2213-2317
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Alcohol use disorders are common both in the United States and globally, and are associated with a variety of co-morbid, inflammation-linked diseases. The pathogenesis of many of these ailments are driven by the activation of the NLRP3 inflammasome, a multi-protein intracellular pattern recognition receptor complex that facilitates the cleavage and secretion of the pro-inflammatory cytokines IL-1ß and IL-18. We hypothesized that protracted exposure of leukocytes to ethanol would amplify inflammasome activation, which would help to implicate mechanisms involved in diseases associated with both alcoholism and aberrant NLRP3 inflammasome activation. Here we show that long-term ethanol exposure of human peripheral blood mononuclear cells and a mouse macrophage cell line (J774) amplifies IL-1ß secretion following stimulation with NLRP3 agonists, but not with AIM2 or NLRP1b agonists. The augmented NRLP3 activation was mediated by increases in iNOS expression and NO production, in conjunction with increases in mitochondrial membrane depolarization, oxygen consumption rate, and ROS generation in J774 cells chronically exposed to ethanol (CE cells), effects that could be inhibited by the iNOS inhibitor SEITU, the NO scavenger carboxy-PTIO, and the mitochondrial ROS scavenger MitoQ. Chronic ethanol exposure did not alter K efflux or Zn homeostasis in CE cells, although it did result in a lower intracellular concentration of NAD . Prolonged administration of acetaldehyde, the product of alcohol dehydrogenase (ADH) mediated metabolism of ethanol, mimicked chronic ethanol exposure, whereas ADH inhibition prevented ethanol-induced IL-1ß hypersecretion. Together, these results indicate that increases in iNOS and mitochondrial ROS production are critical for chronic ethanol-induced IL-1ß hypersecretion, and that protracted exposure to the products of ethanol metabolism are probable mediators of NLRP3 inflammasome hyperactivation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1705
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Process

  6 / 84590 MEDLINE  
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[PMID]: 29523925
[Au] Autor:Unterrainer M; Mahler C; Vomacka L; Lindner S; Havla J; Brendel M; Böning G; Ertl-Wagner B; Kümpfel T; Milenkovic VM; Rupprecht R; Kerschensteiner M; Bartenstein P; Albert NL
[Ad] Address:Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians University Munich, Marchioninistr. 15, 81377, Munich, Germany.
[Ti] Title:TSPO PET with [ F]GE-180 sensitively detects focal neuroinflammation in patients with relapsing-remitting multiple sclerosis.
[So] Source:Eur J Nucl Med Mol Imaging;, 2018 Mar 09.
[Is] ISSN:1619-7089
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:PURPOSE: Expression of the translocator protein (TSPO) is upregulated in activated macrophages/microglia and is considered to be a marker of neuroinflammation. We investigated the novel TSPO ligand [ F]GE-180 in patients with relapsing-remitting multiple sclerosis (RRMS) to determine the feasibility of [ F]GE-180 PET imaging in RRMS patients and to assess its ability to detect active inflammatory lesions in comparison with the current gold standard, contrast-enhanced magnetic resonance imaging (MRI). METHODS: Nineteen RRMS patients were prospectively included in this study. All patients underwent TSPO genotyping and were classified as high-affinity, medium-affinity or low-affinity binders (HAB/MAB/LAB). PET scans were performed after administration of 189 ± 12 MBq [ F]GE-180, and 60-90 min summation images were used for visual analysis and assessment of standardized uptake values (SUV). The frontal nonaffected cortex served as a pseudoreference region (PRR) for evaluation of SUV ratios (SUVR). PET data were correlated with MRI signal abnormalities, i.e. T2 hyperintensity or contrast enhancement (CE). When available, previous MRI data were used to follow the temporal evolution of individual lesions. RESULTS: Focal lesions were identified as hot spots by visual inspection. Such lesions were detected in 17 of the 19 patients and overall 89 [ F]GE-180-positive lesions were found. TSPO genotyping revealed 11 patients with HAB status, 5 with MAB status and 3 with LAB status. There were no associations between underlying binding status (HAB, MAB and LAB) and the signal intensity in either lesions (SUVR 1.87 ± 0.43, 1.95 ± 0.48 and 1.86 ± 0.80, respectively; p = 0.280) or the PRR (SUV 0.36 ± 0.03, 0.40 ± 0.06 and 0.37 ± 0.03, respectively; p = 0.990). Of the 89 [ F]GE-180-positive lesions, 70 showed CE on MRI, while the remainder presented as T2 lesions without CE. SUVR were significantly higher in lesions with CE than in those without (2.00 ± 0.53 vs. 1.60 ± 0.15; p = 0.001). Notably, of 19 [ F]GE-180-positive lesions without CE, 8 previously showed CE, indicating that [ F]GE-180 imaging may be able to detect lesional activity that is sustained beyond the blood-brain barrier breakdown. CONCLUSION: [ F]GE-180 PET can detect areas of focal macrophage/microglia activation in patients with RRMS in lesions with and without CE on MRI. Therefore, [ F]GE-180 PET imaging is a sensitive and quantitative approach to the detection of active MS lesions. It may provide information beyond contrast-enhanced MRI and is readily applicable to all patients. [ F]GE-180 PET imaging is therefore a promising new tool for the assessment of focal inflammatory activity in MS.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher
[do] DOI:10.1007/s00259-018-3974-7

  7 / 84590 MEDLINE  
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[PMID]: 29523595
[Au] Autor:Liu C; Zhang C; Jia L; Chen B; Liu L; Sun J; Zhang W; You B; Li Y; Li P; Du J
[Ad] Address:Anzhen Hospital, Beijing, China.
[Ti] Title:Interleukin-3 stimulates matrix metalloproteinase 12 production from macrophages promoting thoracic aortic aneurysm/dissection.
[So] Source:Clin Sci (Lond);, 2018 Mar 09.
[Is] ISSN:1470-8736
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Thoracic aortic aneurysm and dissection (TAAD) is due to degeneration of the aorta and causes a high mortality rate, while molecular mechanisms for the development of TAAD are still not completely understood. In this study, 3-aminopropionitrile (BAPN) treatment was used to induce TAAD mouse model. Through transcriptome analysis, we found the expression levels of genes associated with interleukin-3 (IL-3) signaling pathway were upregulated during TAAD development in mouse, which were validated by real-time PCR. IL-3 positive cells were increased in TAAD mouse aortas, especially for smooth muscle cells (SMCs). IL-3 deficiency reduced BAPN-induced TAAD formation. We then examined the matrix metalloproteinases (MMPs) expression during TAAD formation in both wild-type and IL-3 deficient mice, showing that MMP12 were significantly downregulated in IL-3 deficient aortas. Mechanistically, we found recombination IL-3 could increase MMP12 production and activity from macrophages Silencing of IL-3 receptor ß, which was mainly expressed in macrophages but not SMCs, diminished the activation of c-Jun N terminal kinase (JNK)/extracellular regulated protein kinases 1/2 (ERK1/2)/AP-1 signals, and decreased MMP12 expression in IL-3 stimulated macrophages. Moreover, both circulating and aortic inflammation were decreased in IL-3 deficient aortas. Taken together, our results demonstrated that IL-3 stimulated the production of MMP12 from macrophages by a JNK- and ERK1/2- dependent AP-1 pathway, contributing to TAAD formation. Thus, the IL-3/IL-3Rß/MMP12 signals activation may be an important pathological mechanism for progression of TAAD.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  8 / 84590 MEDLINE  
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[PMID]: 29523554
[Au] Autor:Viaud M; Ivanov S; Vujic N; Duta-Mare M; Aira LE; Barouillet T; Garcia E; Orange F; Dugail I; Hainault I; Stehlik C; Marchetti S; Boyer L; Guinamard R; Foufelle F; Bochem AE; Hovingh KG; Thorp EB; Gautier EL; Kratky D; Da Silva-Jardine PA; Yvan-Charvet L
[Ad] Address:Bâtiment Universitaire ARCHIMED, INSERM U1065.
[Ti] Title:Lysosomal Cholesterol Hydrolysis Couples Efferocytosis to Anti-Inflammatory Oxysterol Production.
[So] Source:Circ Res;, 2018 Mar 09.
[Is] ISSN:1524-4571
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Macrophages face a substantial amount of cholesterol following the ingestion of apoptotic cells and the lysosomal acid lipase (LIPA) has a major role in hydrolyzing cholesteryl esters in the endocytic compartment. Here, we directly investigated the role of LIPA-mediated clearance of apoptotic cells both in vitro and in vivo. We show that LIPA inhibition causes a defective efferocytic response due to impaired generation of 25-OHC and 27-OHC. Reduced synthesis of 25-OHC after LIPA inhibition contributed to defective mitochondria associated membrane (MAM) leading to mitochondrial oxidative stress-induced NLRP3 inflammasome activation and caspase 1-dependent Rac1 degradation. A secondary event consisting of failure to appropriately activate liver X receptor-mediated pathways led to mitigation of cholesterol efflux and apoptotic cell clearance. In mice, LIPA inhibition caused defective clearance of apoptotic lymphocytes and stressed erythrocytes by hepatic and splenic macrophages, culminating in splenomegaly and splenic iron accumulation under hypercholesterolemia. Our findings position lysosomal cholesterol hydrolysis as a critical process that prevents metabolic inflammation by enabling efficient macrophage apoptotic cell clearance.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  9 / 84590 MEDLINE  
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[PMID]: 29482836
[Au] Autor:Kiss M; Van Gassen S; Movahedi K; Saeys Y; Laoui D
[Ad] Address:Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Laboratory of Myeloid Cell Immunology, VIB Center for Inflammation Research, Brussels, Belgium. Electronic address: mate.kiss@vub.be.
[Ti] Title:Myeloid cell heterogeneity in cancer: not a single cell alike.
[So] Source:Cell Immunol;, 2018 Feb 14.
[Is] ISSN:1090-2163
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Tumors of various histological origins show abundant infiltration of myeloid cells from early stages of disease progression. These cells have a profound impact on antitumor immunity and influence fundamental processes that underlie malignancy, including neoangiogenesis, sustained cancer cell proliferation, metastasis and therapy resistance. For these reasons, development of therapeutic approaches to deplete or reprogram myeloid cells in cancer is an emerging field of interest. However, knowledge about the heterogeneity of myeloid cells in tumors and their variability between patients and disease stages is still limited. In this review, we summarize the most recent advances in our understanding about how the phenotype of tumor-associated macrophages, monocytes, neutrophils, myeloid-derived suppressor cells and dendritic cells is dictated by their ontogeny, activation status and localization. We also outline major open questions that will only be resolved by applying high-dimensional single-cell technologies and systems biology approaches in the analysis of the tumor microenvironment.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1802
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  10 / 84590 MEDLINE  
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[PMID]: 29358328
[Au] Autor:Bhagyaraj E; Tiwari D; Ahuja N; Nanduri R; Saini A; Kalra R; Kumar S; Janmeja AK; Gupta P
[Ad] Address:From the Department of Molecular Biology, CSIR-Institute of Microbial Technology, Sector 39 A, Chandigarh 160036 and.
[Ti] Title:A human xenobiotic nuclear receptor contributes to nonresponsiveness of to the antituberculosis drug rifampicin.
[So] Source:J Biol Chem;293(10):3747-3757, 2018 Mar 09.
[Is] ISSN:1083-351X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:is the causative agent of tuberculosis (TB). It acquires phenotypic drug resistance inside macrophages, and this resistance mainly arises from host-induced stress. However, whether cellular drug-efflux mechanisms in macrophages contribute to nonresponsiveness of to anti-TB drugs is unclear. Here, we report that xenobiotic nuclear receptors mediate TB drug nonresponsiveness by modulating drug-efflux transporters in macrophages. This was evident from expression analysis of drug-efflux transporters in macrophages isolated from TB patients. Among patients harboring rifampicin-susceptible we observed increased intracellular survival of upon rifampicin treatment of macrophages isolated from patients not responding to anti-TB drugs compared with macrophages from patients who did respond. Of note, infection and rifampicin exposure synergistically modulated macrophage drug-efflux transporters We also found that the xenobiotic nuclear receptor pregnane X receptor (PXR) modulates macrophage drug-efflux transporter expression and activity, which compromised the anti-TB efficacy of rifampicin. We further validated this finding in a TB mouse model in which use of the PXR antagonist ketoconazole rescued rifampicin anti-TB activity. We conclude that PXR activation in macrophages compromises the efficacy of the anti-TB drug rifampicin. Alternative therapeutic strategies, such as use of the rifampicin derivatives rifapentine and rifabutin, which do not activate PXR, or of a PXR antagonist, may be effective for tackling drug nonresponsiveness of that arises from drug-efflux systems of the host.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:In-Data-Review
[do] DOI:10.1074/jbc.M117.818377


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