{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T09:34:53Z","timestamp":1776850493227,"version":"3.51.2"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,8,30]],"date-time":"2016-08-30T00:00:00Z","timestamp":1472515200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,8,30]],"date-time":"2016-08-30T00:00:00Z","timestamp":1472515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cathepsins are proteolytic enzymes that function in the endocytic pathway, especially in lysosomes, where they contribute directly to pathogen killing or indirectly, by their involvement in the antigen presentation pathways. <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (MTB) is a facultative intracellular pathogen that survives inside the macrophage phagosomes by inhibiting their maturation to phagolysosomes and thus avoiding a low pH and protease-rich environment. We previously showed that mycobacterial inhibition of the proinflammatory transcription factor NF-\u03baB results in impaired delivery of lysosomal enzymes to phagosomes and reduced pathogen killing. Here, we elucidate how MTB also controls cathepsins and their inhibitors, cystatins, at the level of gene expression and proteolytic activity. MTB induced a general down-regulation of cathepsin expression in infected cells, and inhibited IFN\u03b3-mediated increase of cathepsin mRNA. We further show that a decrease in cathepsins B, S and L favours bacterial survival within human primary macrophages. A siRNA knockdown screen of a large set of cathepsins revealed that almost half of these enzymes have a role in pathogen killing, while only cathepsin F coincided with MTB resilience. Overall, we show that cathepsins are important for the control of MTB infection, and as a response, it manipulates their expression and activity to favour its intracellular survival.<\/jats:p>","DOI":"10.1038\/srep32247","type":"journal-article","created":{"date-parts":[[2016,8,30]],"date-time":"2016-08-30T09:38:52Z","timestamp":1472549932000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Role of Cathepsins in Mycobacterium tuberculosis Survival in Human Macrophages"],"prefix":"10.1038","volume":"6","author":[{"given":"David","family":"Pires","sequence":"first","affiliation":[]},{"given":"Joana","family":"Marques","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o Palma","family":"Pombo","sequence":"additional","affiliation":[]},{"given":"Nuno","family":"Carmo","sequence":"additional","affiliation":[]},{"given":"Paulo","family":"Bettencourt","sequence":"additional","affiliation":[]},{"given":"Olivier","family":"Neyrolles","sequence":"additional","affiliation":[]},{"given":"Geanncarlo","family":"Lugo-Villarino","sequence":"additional","affiliation":[]},{"given":"Elsa","family":"Anes","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2016,8,30]]},"reference":[{"key":"BFsrep32247_CR1","unstructured":"WHO. Global Tuberculosis Report 2013. World Health Organization (World Health Organization Press, 2013)."},{"key":"BFsrep32247_CR2","doi-asserted-by":"publisher","first-page":"e16161","DOI":"10.1371\/journal.pone.0016161","volume":"6","author":"DD Kang","year":"2011","unstructured":"Kang, D. D., Lin, Y., Moreno, J.-R., Randall, T. D. & Khader, S. A. Profiling early lung immune responses in the mouse model of tuberculosis. PLoS One 6, e16161 (2011).","journal-title":"PLoS One"},{"key":"BFsrep32247_CR3","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1038\/nri2591","volume":"9","author":"DG Russell","year":"2009","unstructured":"Russell, D. G., Vanderven, B. C., Glennie, S., Mwandumba, H. & Heyderman, R. S. The macrophage marches on its phagosome: dynamic assays of phagosome function. Nat. Rev. Immunol. 9, 594\u2013600 (2009).","journal-title":"Nat. Rev. Immunol."},{"key":"BFsrep32247_CR4","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1038\/35085034","volume":"2","author":"DG Russell","year":"2001","unstructured":"Russell, D. G. Mycobacterium tuberculosis: here today, and here tomorrow. Nat. Rev. Mol. Cell Biol. 2, 569\u2013577 (2001).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"BFsrep32247_CR5","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1111\/j.1462-5822.2006.00705.x","volume":"8","author":"V Deretic","year":"2006","unstructured":"Deretic, V. et al. Mycobacterium tuberculosis inhibition of phagolysosome biogenesis and autophagy as a host defence mechanism. Cell. Microbiol. 8, 719\u2013727 (2006).","journal-title":"Cell. Microbiol."},{"key":"BFsrep32247_CR6","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1084\/jem.134.3.713","volume":"134","author":"JA Armstrong","year":"1971","unstructured":"Armstrong, J. A. & Hart, P. D. Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J. Exp. Med. 134, 713\u2013740 (1971).","journal-title":"J. Exp. Med."},{"key":"BFsrep32247_CR7","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1084\/jem.181.1.257","volume":"181","author":"DL Clemens","year":"1995","unstructured":"Clemens, D. L. & Horwitz, M. A. Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited. J. Exp. Med. 181, 257\u2013270 (1995).","journal-title":"J. Exp. Med."},{"key":"BFsrep32247_CR8","first-page":"529","volume":"10","author":"L Jordao","year":"2008","unstructured":"Jordao, L., Bleck, C. K. E., Mayorga, L., Griffiths, G. & Anes, E. On the killing of mycobacteria by macrophages. Cell. Microbiol. 10, 529\u2013548 (2008).","journal-title":"Cell. Microbiol."},{"key":"BFsrep32247_CR9","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1146\/annurev.immunol.021908.132703","volume":"27","author":"AM Cooper","year":"2009","unstructured":"Cooper, A. M. Cell-mediated immune responses in tuberculosis. Annu. Rev. Immunol. 27, 393\u2013422 (2009).","journal-title":"Annu. Rev. Immunol."},{"key":"BFsrep32247_CR10","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/j.cell.2004.11.038","volume":"119","author":"MG Gutierrez","year":"2004","unstructured":"Gutierrez, M. G. et al. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119, 753\u2013766 (2004).","journal-title":"Cell"},{"key":"BFsrep32247_CR11","doi-asserted-by":"publisher","first-page":"2768","DOI":"10.1111\/j.1462-5822.2007.01039.x","volume":"9","author":"GE Purdy","year":"2007","unstructured":"Purdy, G. E. & Russell, D. G. Lysosomal ubiquitin and the demise of mycobacterium tuberculosis. Cell. Microbiol. 9, 2768\u20132774 (2007).","journal-title":"Cell. Microbiol."},{"key":"BFsrep32247_CR12","doi-asserted-by":"crossref","unstructured":"Herbst, S., Schaible, U. E. & Schneider, B. E. Interferon gamma activated macrophages kill mycobacteria by nitric oxide induced apoptosis. PLoS One 6 (2011).","DOI":"10.1371\/journal.pone.0019105"},{"key":"BFsrep32247_CR13","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/ncb1036","volume":"5","author":"E Anes","year":"2003","unstructured":"Anes, E. et al. Selected lipids activate phagosome actin assembly and maturation resulting in killing of pathogenic mycobacteria. Nat. Cell Biol. 5, 793\u2013802 (2003).","journal-title":"Nat. Cell Biol."},{"key":"BFsrep32247_CR14","doi-asserted-by":"publisher","first-page":"2651","DOI":"10.4049\/jimmunol.181.4.2651","volume":"181","author":"MG Gutierrez","year":"2008","unstructured":"Gutierrez, M. G. et al. NF-kappa B activation controls phagolysosome fusion-mediated killing of mycobacteria by macrophages. J. Immunol. 181, 2651\u20132663 (2008).","journal-title":"J. Immunol."},{"key":"BFsrep32247_CR15","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1111\/j.1462-5822.2008.01263.x","volume":"11","author":"MG Gutierrez","year":"2009","unstructured":"Gutierrez, M. G., Gonzalez, A. P., Anes, E. & Griffiths, G. Role of lipids in killing mycobacteria by macrophages: Evidence for NF-\u03baB-dependent and -independent killing induced by different lipids. Cell. Microbiol. 11, 406\u2013420 (2009).","journal-title":"Cell. Microbiol."},{"key":"BFsrep32247_CR16","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.micinf.2011.03.002","volume":"13","author":"SM Behar","year":"2011","unstructured":"Behar, S. M., Martin, C. J., Nunes-Alves, C., Divangahi, M. & Remold, H. G. Lipids, apoptosis, and cross-presentation: links in the chain of host defense against Mycobacterium tuberculosis. Microbes Infect. 13, 749\u2013756 (2011).","journal-title":"Microbes Infect."},{"key":"BFsrep32247_CR17","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.immuni.2005.12.001","volume":"24","author":"F Winau","year":"2006","unstructured":"Winau, F. et al. Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis. Immunity 24, 105\u2013117 (2006).","journal-title":"Immunity"},{"key":"BFsrep32247_CR18","doi-asserted-by":"publisher","first-page":"6031","DOI":"10.1073\/pnas.0700036104","volume":"104","author":"S Alonso","year":"2007","unstructured":"Alonso, S., Pethe, K., Russell, D. G. & Purdy, G. E. Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy. Proc. Natl. Acad. Sci. USA 104, 6031\u20136036 (2007).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFsrep32247_CR19","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.bbapap.2011.10.002","volume":"1824","author":"V Turk","year":"2012","unstructured":"Turk, V. et al. Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochim. Biophys. Acta 1824, 68\u201388 (2012).","journal-title":"Biochim. Biophys. Acta"},{"key":"BFsrep32247_CR20","first-page":"w13042","volume":"140","author":"S Conus","year":"2010","unstructured":"Conus, S. & Simon, H.-U. Cathepsins and their involvement in immune responses. Swiss Med. Wkly. 140, w13042 (2010).","journal-title":"Swiss Med. Wkly."},{"key":"BFsrep32247_CR21","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1038\/srep00739","volume":"2","author":"CR Hole","year":"2012","unstructured":"Hole, C. R., Bui, H., Wormley, F. L. & Wozniak, K. L. Mechanisms of dendritic cell lysosomal killing of Cryptococcus. Sci. Rep. 2, 739 (2012).","journal-title":"Sci. Rep."},{"key":"BFsrep32247_CR22","doi-asserted-by":"publisher","first-page":"e1001262","DOI":"10.1371\/journal.ppat.1001262","volume":"7","author":"M Bewley","year":"2011","unstructured":"Bewley, M. a et al. A cardinal role for cathepsin d in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci. PLoS Pathog. 7, e1001262 (2011).","journal-title":"PLoS Pathog."},{"key":"BFsrep32247_CR23","doi-asserted-by":"publisher","first-page":"4476","DOI":"10.4049\/jimmunol.1103346","volume":"188","author":"K Steinwede","year":"2012","unstructured":"Steinwede, K. et al. Cathepsin G and neutrophil elastase contribute to lung-protective immunity against mycobacterial infections in mice. J. Immunol. 188, 4476\u20134487 (2012).","journal-title":"J. Immunol."},{"key":"BFsrep32247_CR24","doi-asserted-by":"publisher","first-page":"5712","DOI":"10.1128\/IAI.72.10.5712-5721.2004","volume":"72","author":"CA Rivera-Marrero","year":"2004","unstructured":"Rivera-Marrero, C. A., Stewart, J., Shafer, W. M. & Roman, J. The down-regulation of cathepsin G in THP-1 monocytes after infection with Mycobacterium tuberculosis is associated with increased intracellular survival of bacilli. Infect. Immun. 72, 5712\u20135721 (2004).","journal-title":"Infect. Immun."},{"key":"BFsrep32247_CR25","doi-asserted-by":"publisher","first-page":"5137","DOI":"10.4049\/jimmunol.179.8.5137","volume":"179","author":"H Soualhine","year":"2007","unstructured":"Soualhine, H. et al. Mycobacterium bovis bacillus Calmette-Gu\u00e9rin secreting active cathepsin S stimulates expression of mature MHC class II molecules and antigen presentation in human macrophages. J. Immunol. 179, 5137\u20135145 (2007).","journal-title":"J. Immunol."},{"key":"BFsrep32247_CR26","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1111\/j.0105-2896.2005.00310.x","volume":"207","author":"LC Hsing","year":"2005","unstructured":"Hsing, L. C. & Rudensky, A. Y. The lysosomal cysteine proteases in MHC class II antigen presentation. Immunol. Rev. 207, 229\u2013241 (2005).","journal-title":"Immunol. Rev."},{"key":"BFsrep32247_CR27","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/S1074-7613(00)80176-4","volume":"12","author":"JA Villadangos","year":"2000","unstructured":"Villadangos, J. A. & Ploegh, H. L. Proteolysis in MHC class II antigen presentation: who\u2019s in charge? Immunity 12, 233\u2013239 (2000).","journal-title":"Immunity"},{"key":"BFsrep32247_CR28","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.4049\/jimmunol.174.3.1205","volume":"174","author":"C Beers","year":"2005","unstructured":"Beers, C. et al. Cathepsin S controls MHC class II-mediated antigen presentation by epithelial cells in vivo . J. Immunol. 174, 1205\u20131212 (2005).","journal-title":"J. Immunol."},{"key":"BFsrep32247_CR29","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1084\/jem.191.7.1177","volume":"191","author":"GP Shi","year":"2000","unstructured":"Shi, G. P. et al. Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages. J. Exp. Med. 191, 1177\u20131186 (2000).","journal-title":"J. Exp. Med."},{"key":"BFsrep32247_CR30","doi-asserted-by":"publisher","first-page":"2309","DOI":"10.1128\/MCB.26.6.2309-2316.2006","volume":"26","author":"C-H Tang","year":"2006","unstructured":"Tang, C.-H. et al. Murine cathepsin F deficiency causes neuronal lipofuscinosis and late-onset neurological disease. Mol. Cell. Biol. 26, 2309\u20132316 (2006).","journal-title":"Mol. Cell. Biol."},{"key":"BFsrep32247_CR31","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1111\/j.1600-0854.2006.00528.x","volume":"8","author":"RM Yates","year":"2007","unstructured":"Yates, R. M., Hermetter, A., Taylor, G. a & Russell, D. G. Macrophage activation downregulates the degradative capacity of the phagosome. Traffic 8, 241\u2013250 (2007).","journal-title":"Traffic"},{"key":"BFsrep32247_CR32","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.cell.2006.05.035","volume":"126","author":"A Savina","year":"2006","unstructured":"Savina, A. et al. NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. Cell 126, 205\u2013218 (2006).","journal-title":"Cell"},{"key":"BFsrep32247_CR33","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1111\/j.1600-065X.2007.00552.x","volume":"219","author":"A Savina","year":"2007","unstructured":"Savina, A. & Amigorena, S. Phagocytosis and antigen presentation in dendritic cells. Immunol. Rev. 219, 143\u2013156 (2007).","journal-title":"Immunol. Rev."},{"key":"BFsrep32247_CR34","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1016\/S0092-8674(00)81458-0","volume":"93","author":"P Pierre","year":"1998","unstructured":"Pierre, P. & Mellman, I. Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells. Cell 93, 1135\u20131145 (1998).","journal-title":"Cell"},{"key":"BFsrep32247_CR35","doi-asserted-by":"crossref","unstructured":"Simeone, R. et al. Phagosomal rupture by Mycobacterium tuberculosis results in toxicity and host cell death. PLoS Pathog. 8 (2012).","DOI":"10.1371\/journal.ppat.1002507"},{"key":"BFsrep32247_CR36","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1111\/j.1462-5822.2010.01450.x","volume":"12","author":"BB Mishra","year":"2010","unstructured":"Mishra, B. B. et al. Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the NLRP3\/ASC inflammasome. Cell. Microbiol. 12, 1046\u20131063 (2010).","journal-title":"Cell. Microbiol."},{"key":"BFsrep32247_CR37","doi-asserted-by":"publisher","first-page":"e20302","DOI":"10.1371\/journal.pone.0020302","volume":"6","author":"A Welin","year":"2011","unstructured":"Welin, A., Eklund, D., Stendahl, O. & Lerm, M. Human macrophages infected with a high burden of ESAT-6-expressing M. tuberculosis undergo caspase-1- and cathepsin B-independent necrosis. PLoS One 6, e20302 (2011).","journal-title":"PLoS One"},{"key":"BFsrep32247_CR38","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.tube.2010.09.002","volume":"90","author":"M Altaf","year":"2010","unstructured":"Altaf, M., Miller, C. H., Bellows, D. S. & O\u2019Toole, R. Evaluation of the Mycobacterium smegmatis and BCG models for the discovery of Mycobacterium tuberculosis inhibitors. Tuberculosis (Edinb). 90, 333\u2013337 (2010).","journal-title":"Tuberculosis (Edinb)."},{"key":"BFsrep32247_CR39","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1194\/jlr.M400308-JLR200","volume":"46","author":"C Villeneuve","year":"2005","unstructured":"Villeneuve, C. et al. Mycobacteria use their surface-exposed glycolipids to infect human macrophages through a receptor-dependent process. J. Lipid Res. 46, 475\u2013483 (2005).","journal-title":"J. Lipid Res."},{"key":"BFsrep32247_CR40","doi-asserted-by":"publisher","first-page":"e1403","DOI":"10.1371\/journal.pone.0001403","volume":"3","author":"L Tailleux","year":"2008","unstructured":"Tailleux, L. et al. Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages. PLoS One 3, e1403 (2008).","journal-title":"PLoS One"},{"key":"BFsrep32247_CR41","first-page":"523","volume":"42","author":"K Hanada","year":"1978","unstructured":"Hanada, K. et al. Isolation and Characterization of E\u201364, a New Thiol Protease Inhibitor. Agric. Biol. Chem. 42, 523\u2013528 (1978).","journal-title":"Agric. Biol. Chem."},{"key":"BFsrep32247_CR42","doi-asserted-by":"publisher","first-page":"D503","DOI":"10.1093\/nar\/gkt953","volume":"42","author":"ND Rawlings","year":"2014","unstructured":"Rawlings, N. D., Waller, M., Barrett, A. J. & Bateman, A. MEROPS: the database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Res. 42, D503\u2013D509 (2014).","journal-title":"Nucleic Acids Res."},{"key":"BFsrep32247_CR43","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.biochi.2007.07.024","volume":"90","author":"K Brix","year":"2008","unstructured":"Brix, K., Dunkhorst, A., Mayer, K. & Jordans, S. Cysteine cathepsins: cellular roadmap to different functions. Biochimie 90, 194\u2013207 (2008).","journal-title":"Biochimie"},{"key":"BFsrep32247_CR44","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1084\/jem.20020978","volume":"197","author":"C Beers","year":"2003","unstructured":"Beers, C., Honey, K., Fink, S., Forbush, K. & Rudensky, a. Differential Regulation of Cathepsin S and Cathepsin L in Interferon -treated Macrophages. J. Exp. Med. 197, 169\u2013179 (2003).","journal-title":"J. Exp. Med."},{"key":"BFsrep32247_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1084\/jem.142.1.1","volume":"142","author":"JA Armstrong","year":"1975","unstructured":"Armstrong, J. A. & Hart, P. D. Phagosome-lysosome interactions in cultured macrophages infected with virulent tubercle bacilli. Reversal of the usual nonfusion pattern and observations on bacterial survival. J. Exp. Med. 142, 1\u201316 (1975).","journal-title":"J. Exp. Med."},{"key":"BFsrep32247_CR46","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1111\/j.1462-5822.2010.01544.x","volume":"13","author":"MN Brooks","year":"2011","unstructured":"Brooks, M. N. et al. NOD2 controls the nature of the inflammatory response and subsequent fate of Mycobacterium tuberculosis and M. bovis BCG in human macrophages. Cell. Microbiol. 13, 402\u2013418 (2011).","journal-title":"Cell. Microbiol."},{"key":"BFsrep32247_CR47","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/3-540-37673-9_5","volume":"56","author":"A Rudensky","year":"2005","unstructured":"Rudensky, A. & Beers, C. In Cytokines as Potential Therapeutic Targets for Inflammatory Skin Diseases (eds Numerof, R., Dinarello, C. A. & Asadullah, K. ) 56, 81\u201395 (Springer Berlin Heidelberg, 2005).","journal-title":"Cytokines as Potential Therapeutic Targets for Inflammatory Skin Diseases"},{"key":"BFsrep32247_CR48","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1111\/cmi.12092","volume":"15","author":"M Podinovskaia","year":"2013","unstructured":"Podinovskaia, M., Lee, W., Caldwell, S. & Russell, D. G. Infection of macrophages with Mycobacterium tuberculosis induces global modifications to phagosomal function. Cell. Microbiol. 15, 843\u2013859 (2013).","journal-title":"Cell. Microbiol."},{"key":"BFsrep32247_CR49","doi-asserted-by":"publisher","first-page":"9842","DOI":"10.1074\/jbc.273.16.9842","volume":"273","author":"V Claus","year":"1998","unstructured":"Claus, V. et al. Lysosomal enzyme trafficking between phagosomes, endosomes, and lysosomes in J774 macrophages. Enrichment of cathepsin H in early endosomes. J. Biol. Chem. 273, 9842\u20139851 (1998).","journal-title":"J. Biol. Chem."},{"key":"BFsrep32247_CR50","doi-asserted-by":"publisher","first-page":"3348","DOI":"10.1002\/1521-4141(200212)32:12<3348::AID-IMMU3348>3.0.CO;2-S","volume":"32","author":"A Lautwein","year":"2002","unstructured":"Lautwein, A. et al. Inflammatory stimuli recruit cathepsin activity to late endosomal compartments in human dendritic cells. Eur. J. Immunol. 32, 3348\u20133357 (2002).","journal-title":"Eur. J. Immunol."},{"key":"BFsrep32247_CR51","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.chom.2007.07.009","volume":"2","author":"SB Willingham","year":"2007","unstructured":"Willingham, S. B. et al. Microbial pathogen-induced necrotic cell death mediated by the inflammasome components CIAS1\/cryopyrin\/NLRP3 and ASC. Cell Host Microbe 2, 147\u2013159 (2007).","journal-title":"Cell Host Microbe"},{"key":"BFsrep32247_CR52","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1093\/intimm\/dxl029","volume":"18","author":"RM Nepal","year":"2006","unstructured":"Nepal, R. M., Mampe, S., Shaffer, B., Erickson, A. H. & Bryant, P. Cathepsin L maturation and activity is impaired in macrophages harboring M. avium and M. tuberculosis. Int. Immunol. 18, 931\u2013939 (2006).","journal-title":"Int. Immunol."},{"key":"BFsrep32247_CR53","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1111\/j.1600-065X.2010.00984.x","volume":"240","author":"DG Russell","year":"2011","unstructured":"Russell, D. G. Mycobacterium tuberculosis and the intimate discourse of a chronic infection. Immunol. Rev. 240, 252\u2013268 (2011).","journal-title":"Immunol. Rev."},{"key":"BFsrep32247_CR54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1034\/j.1600-0854.2000.010306.x","volume":"1","author":"WL Beatty","year":"2000","unstructured":"Beatty, W. L. et al. Trafficking and release of mycobacterial lipids from Infected Macrophages. Traffic 1, 1\u201313 (2000).","journal-title":"Traffic"},{"key":"BFsrep32247_CR55","doi-asserted-by":"publisher","first-page":"e105","DOI":"10.1371\/journal.ppat.0030105","volume":"3","author":"B McLaughlin","year":"2007","unstructured":"McLaughlin, B. et al. A mycobacterium ESX-1-secreted virulence factor with unique requirements for export. PLoS Pathog. 3, e105 (2007).","journal-title":"PLoS Pathog."},{"key":"BFsrep32247_CR56","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.4161\/auto.20881","volume":"8","author":"A Romagnoli","year":"2012","unstructured":"Romagnoli, A. et al. ESX-1 dependent impairment of autophagic flux by Mycobacterium tuberculosis in human dendritic cells. Autophagy 8, 1357\u20131370 (2012).","journal-title":"Autophagy"},{"key":"BFsrep32247_CR57","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1111\/j.1600-0854.2005.00284.x","volume":"6","author":"RM Yates","year":"2005","unstructured":"Yates, R. M., Hermetter, A. & Russell, D. G. The kinetics of phagosome maturation as a function of phagosome\/lysosome fusion and acquisition of hydrolytic activity. Traffic 6, 413\u2013420 (2005).","journal-title":"Traffic"},{"key":"BFsrep32247_CR58","doi-asserted-by":"publisher","first-page":"e13594","DOI":"10.1371\/journal.pone.0013594","volume":"5","author":"C Wang","year":"2010","unstructured":"Wang, C. et al. Innate immune response to Mycobacterium tuberculosis Beijing and other genotypes. PLoS One 5, e13594 (2010).","journal-title":"PLoS One"},{"key":"BFsrep32247_CR59","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider, C. A., Rasband, W. S. & Eliceiri, K. W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods 9, 671\u2013675 (2012).","journal-title":"Nat. Methods"},{"key":"BFsrep32247_CR60","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/icb.2014.39","volume":"92","author":"A Troegeler","year":"2014","unstructured":"Troegeler, A. et al. An efficient siRNA-mediated gene silencing in primary human monocytes, dendritic cells and macrophages. Immunol. Cell Biol. 92, 699\u2013708 (2014).","journal-title":"Immunol. Cell Biol."},{"key":"BFsrep32247_CR61","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1016\/j.cell.2006.01.040","volume":"124","author":"J Moffat","year":"2006","unstructured":"Moffat, J. et al. A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 124, 1283\u20131298 (2006).","journal-title":"Cell"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep32247.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep32247","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep32247.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T06:04:03Z","timestamp":1672898643000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep32247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,30]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,8,31]]}},"alternative-id":["BFsrep32247"],"URL":"https:\/\/doi.org\/10.1038\/srep32247","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,30]]},"assertion":[{"value":"12 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"32247"}}