Immune Control of Tuberculosis by IFN-γ-Inducible LRG-47
Open accessAbstract
Interferon-γ (IFN-γ) provides an essential component of immunity to tuberculosis by activating infected host macrophages to directly inhibit the replication of Mycobacterium tuberculosis ( Mtb ). IFN-γ–inducible nitric oxide synthase 2 (NOS2) is considered a principal effector mechanism, although other pathways may also exist. Here, we identify one member of a newly emerging 47-kilodalton (p47) guanosine triphosphatase family, LRG-47, that acts independently of NOS2 to protect against disease. Mice lacking LRG-47 failed to control Mtb replication, unlike those missing the related p47 guanosine triphosphatases IRG-47 or IGTP. Defective bacterial killing in IFN-γ–activated LRG-47 –/– macrophages was associated with impaired maturation of Mtb -containing phagosomes, vesicles that otherwise recruited LRG-47 in wild-type cells. Thus, LRG-47 may serve as a critical vacuolar trafficking component used to dispose of intracellular pathogens like Mtb .
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Upon stimulation with IFN-γ, macrophages activate GTPases responsible for the recruitment of NOX2 to the mycobacterial phagosome.
“Upon stimulation with IFN-γ, macrophages activate GTPases, which are responsible for the recruitment of NOX2 to the mycobacterial phagosome (62, 63).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [63]
Cites
NITRIC OXIDE AND MACROPHAGE FUNCTION
MacMicking, J. D., Xie, Q. W., & Nathan, C. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.323 · Cited by 4,184 · see citing works
Self-citationDarnell, J. E. (1997) · Science · doi:10.1126/science.277.5332.1630 · Cited by 3,979 · see citing works
CELLULAR RESPONSES TO INTERFERON-γ
Boehm, U., Klamp, T., Groot, M., & Howard, J. C. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.749 · Cited by 2,890 · see citing works
Takai, Y., Sasaki, T., & Matozaki, T. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.1.153 · Cited by 2,481 · see citing works
McKinney, J. D., zu Bentrup, K. H., Muñoz‐Elías, E. J., Miczák, A., Chen, B., Chan, W.-T., Swenson, D. L., Sacchettini, J. C., Jacobs, W. R., & Russell, D. G. (2000) · Nature · doi:10.1038/35021074 · Cited by 1,361 · see citing works
Self-citationFlynn, J., & Chan, J. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.93 · Cited by 1,144 · see citing works
Chan, J., Xing, Y., Magliozzo, R. S., & Bloom, B. R. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.175.4.1111 · Cited by 1,062 · see citing works
Genetic Dissection of Immunity to Mycobacteria: The Human Model
Casanova, J., & Abel, L. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.081501.125851 · Cited by 987 · see citing works
Mycobacterium tuberculosis: here today, and here tomorrow
Russell, D. G. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35085034 · Cited by 781 · see citing works
Activation of Lysosomal Function During Dendritic Cell Maturation
Trombetta, E. S., Ebersold, M. W., Garrett, W. S., Pypaert, M., & Mellman, I. (2003) · Science · doi:10.1126/science.1080106 · Cited by 740 · see citing works
Induction of Direct Antimicrobial Activity Through Mammalian Toll-Like Receptors
Thoma-Uszynski, S., Stenger, S., Takeuchi, O., Ochoa, M. T., Engele, M., Sieling, P. A., Barnes, P. F., Röllinghoff, M., Bölcskei, P., Wagner, M., et al. (2001) · Science · doi:10.1126/science.291.5508.1544 · Cited by 729 · see citing works
Takai, Y., Kaibuchi, K., Kikuchi, A., & Kawata, M. (1992) · International review of cytology · doi:10.1016/s0074-7696(08)61861-6 · Cited by 516 · see citing works
Ehrt, S., Schnappinger, D., Bekiranov, S., Drenkow, J., Shi, S., Gingeras, T., Gaasterland, T., Schoolnik, G. K., & Nathan, C. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.8.1123 · Cited by 460 · see citing works
Maintenance of Golgi structure and function depends on the integrity of ER export
Ward, T. H., Polishchuk, R., Caplan, S., Hirschberg, K., & Lippincott‐Schwartz, J. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200107045 · Cited by 419 · see citing works
Biologic consequences of Stat1-independent IFN signaling
Gil, M. P., Bohn, E., O'Guin, A. K., Ramana, C. V., Levine, B., Stark, G. R., Virgin, H. W., & Schreiber, R. D. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111163898 · Cited by 345 · see citing works
Mazurek, G. H. (2001) · JAMA · doi:10.1001/jama.286.14.1740 · Cited by 332 · see citing works
Collazo, C. M., Yap, G. S., Sempowski, G. D., Lusby, K. C., Tessarollo, L., Woude, G. F. V., Sher, A., & Taylor, G. A. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.2.181 · Cited by 325 · see citing works
Self-citationErasing the World's Slow Stain: Strategies to Beat Multidrug-Resistant Tuberculosis
Dye, C., Williams, B. G., Espinal, M., & Raviglione, M. C. (2002) · Science · doi:10.1126/science.1063814 · Cited by 314 · see citing works
Fisher, M. A., Plikaytis, B. B., & Shinnick, T. M. (2002) · Journal of Bacteriology · doi:10.1128/jb.184.14.4025-4032.2002 · Cited by 308 · see citing works
Clemens, D. L., & Horwitz, M. A. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.4.1349 · Cited by 304 · see citing works
Pathogen-specific loss of host resistance in mice lacking the IFN-γ-inducible gene IGTP
Taylor, G. A., Collazo, C. M., Yap, G. S., Nguyen, K., Gregorio, T. A., Taylor, L. S., Eagleson, B., Secrest, L., Southon, E. A., Reid, S. W., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.2.751 · Cited by 265 · see citing works
Self-citationTwo families of GTPases dominate the complex cellular response to IFN-gamma.
Boehm, U., Guethlein, L. A., Klamp, T., Ozbek, K., Schaub, A., Fütterer, A., Pfeffer, K., & Howard, J. C. (1998) · PubMed · Cited by 224 · see citing works
Two Families of GTPases Dominate the Complex Cellular Response to IFN-γ
Boehm, U., Guethlein, L. A., Klamp, T., Ozbek, K., Schaub, A., Fütterer, A., Pfeffer, K., & Howard, J. C. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.12.6715 · Cited by 208 · see citing works
Hart, P. D., & Young, M. R. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.174.4.881 · Cited by 154 · see citing works
Buchmeier, N. A., Blanc‐Potard, A., Ehrt, S., Piddington, D. L., Riley, L. W., & Groisman, E. A. (2000) · Molecular Microbiology · doi:10.1046/j.1365-2958.2000.01797.x · Cited by 150 · see citing works
Olakanmi, O., Schlesinger, L. S., Ahmed, A., & Britigan, B. E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m209768200 · Cited by 122 · see citing works
Kincaid, E., & Ernst, J. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.4.2042 · Cited by 115 · see citing works
The Inducibly Expressed GTPase Localizes to the Endoplasmic Reticulum, Independently of GTP Binding
Taylor, G. A., Stauber, R. H., Rulong, S., Hudson, E., Pei, Y. V., Pavlakis, G. N., Resau, J. H., & Woude, G. F. V. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.16.10639 · Cited by 84 · see citing works
Self-citationHayashi, T., Sriramarao, P., Takabayashi, K., Uden, J. H. V., Kornbluth, R. S., Baird, S. M., Taylor, M. W., Carson, D. A., Catanzaro, A., & Raz, E. (2001) · Infection and Immunity · doi:10.1128/iai.69.10.6156-6164.2001 · Cited by 75 · see citing works
Zerrahn, J., Schaible, U. E., Brinkmann, V., Guhlich‐Bornhof, U., & Kaufmann, S. H. E. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.7.3428 · Cited by 62 · see citing works
Macrophage Immunity and Mycobacterium tuberculosis
MacMicking, J. D., & McKinney, J. D. (2003) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-55742-2_22 · Cited by 2 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Gutierrez, M. G., Master, S. S., Singh, S. B., Taylor, G. A., Colombo, M. I., & Deretic, V. (2004) · Cell · doi:10.1016/j.cell.2004.11.038 · Cited by 2,252 · see citing works
“tuberculosis infection and that this effect was independent of autophagy promotes mycobacterial phagosome maturation and associated intracellular killing of the pathoproduction of reactive nitrogen and oxygen intermediates (MacMicking et al., 2003).”
BackgroundResultInfluentialSelf-citationKaser, A., Zeissig, S., & Blumberg, R. S. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101225 · Cited by 1,806 · see citing works
Khader, S. A., Bell, G. K., Pearl, J. E., Fountain, J. J., Rangel‐Moreno, J., Cilley, G. E., Shen, F., Eaton, S. M., Gaffen, S. L., Swain, S. L., et al. (2007) · Nature Immunology · doi:10.1038/ni1449 · Cited by 1,442 · see citing works
The Immune Response in Tuberculosis
O’Garra, A., Redford, P. S., McNab, F. W., Bloom, C. I., Wilkinson, R. J., & Berry, M. P. R. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095939 · Cited by 1,351 · see citing works
“tuberculosis infection include LRG-47, an IFNinducible GTP-binding protein (275).”
BackgroundCell-Mediated Immune Responses in Tuberculosis
Cooper, A. M. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132703 · Cited by 1,173 · see citing works
Mycobacterial persistence requires the utilization of host cholesterol
Pandey, A. K., & Sassetti, C. M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711159105 · Cited by 1,064 · see citing works
Macrophage defense mechanisms against intracellular bacteria
Weiss, G., & Schaible, U. E. (2015) · Immunological Reviews · doi:10.1111/imr.12266 · Cited by 989 · see citing works
Human IRGM Induces Autophagy to Eliminate Intracellular Mycobacteria
Singh, S. B., Davis, A. S., Taylor, G. A., & Deretic, V. (2006) · Science · doi:10.1126/science.1129577 · Cited by 915 · see citing works
Self-citationRevisiting the role of the granuloma in tuberculosis
Ramakrishnan, L. (2012) · Nature reviews. Immunology · doi:10.1038/nri3211 · Cited by 887 · see citing works
Autophagy, Immunity, and Microbial Adaptations
Deretic, V. P., & Levine, B. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2009.05.016 · Cited by 868 · see citing works
“The p47 GTPase Lrg-47 (Irgm1) links host defense and hematopoietic stem cell proliferation.”
ResultInfluentialHuman RAS Superfamily Proteins and Related GTPases
Colicelli, J. (2004) · Science s STKE · doi:10.1126/stke.2502004re13 · Cited by 837 · see citing works
Toll-like Receptor 4 Is a Sensor for Autophagy Associated with Innate Immunity
Xu, Y., Jagannath, C., Liu, X.-D., Sharafkhaneh, A., Kolodziejska, K. E., & Eissa, N. T. (2007) · Immunity · doi:10.1016/j.immuni.2007.05.022 · Cited by 880 · see citing works
“Furthermore, LPS upregulated LRG47, a GTPase that has been recently shown to be involved in antimycobacterial effects through contribution to autophagy induction (MacMicking et al., 2003; Gutierrez et al., 2004).”
BackgroundWatson, R. O., Manzanillo, P. S., & Cox, J. S. (2012) · Cell · doi:10.1016/j.cell.2012.06.040 · Cited by 755 · see citing works
“Although inducing autophagy exogenously via starvation, treatment with rapamycin, interferon gamma (IFN-g), or vitamin D3 or genetic depletion of autophagy inhibitors can lead to decreased bacterial replication in macrophages (Gutierrez et al., 2004; Kumar et al., 2010; Singh et al., 2006; Yuk et al., 2009), how M. tu…”
Tuberculosis and HIV Co-Infection
Pawlowski, A., Jansson, M., Sköld, M., Rottenberg, M. E., & Källenius, G. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002464 · Cited by 776 · see citing works
“Following activation by cytokines and innate receptor agonists, infected macrophages elicit direct bactericidal effector functions, such as reactive oxygen or nitrogen intermediates [10,11], or expression of small GTPases that can regulate endosomal trafficking [12].”
BackgroundMycobacterium tuberculosis: success through dormancy
Gengenbacher, M., & Kaufmann, S. H. E. (2012) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2012.00331.x · Cited by 698 · see citing works
“0 (Sturgill-Koszycki et al., 1996; MacMicking et al., 2003; Yates et al., 2005).”
BackgroundInfluentialWho puts the tubercle in tuberculosis?
Russell, D. G. (2006) · Nature Reviews Microbiology · doi:10.1038/nrmicro1538 · Cited by 641 · see citing works
Interferon-gamma (IFN-γ): Exploring its implications in infectious diseases
Kak, G., Raza, M., & Tiwari, B. K. (2018) · BioMolecular Concepts · doi:10.1515/bmc-2018-0007 · Cited by 624 · see citing works
Interferon-inducible effector mechanisms in cell-autonomous immunity
MacMicking, J. D. (2012) · Nature reviews. Immunology · doi:10.1038/nri3210 · Cited by 564 · see citing works
Self-citationPersistent bacterial infections: the interface of the pathogen and the host immune system
Monack, D. M., Mueller, A., & Falkow, S. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro955 · Cited by 574 · see citing works
Mechanism of phagolysosome biogenesis block by viable Mycobacterium tuberculosis
Vergne, I., Chua, J., Lee, H.-H., Lucas, M., Belisle, J. T., & Deretic, V. P. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409716102 · Cited by 537 · see citing works
Brest, P., Lapaquette, P., Souidi, M., Lebrigand, K., Cesaro, A., Vouret-Craviari, V., Mari, B., Barbry, P., Mosnier, J.-F., Hébuterne, X., et al. (2011) · Nature Genetics · doi:10.1038/ng.762 · Cited by 563 · see citing works
GBP5 Promotes NLRP3 Inflammasome Assembly and Immunity in Mammals
Shenoy, A. R., Wellington, D. A., Kumar, P., Kassa, H. T., Booth, C. J., Cresswell, P., & MacMicking, J. D. (2012) · Science · doi:10.1126/science.1217141 · Cited by 512 · see citing works
Self-citationA Family of IFN-γ–Inducible 65-kD GTPases Protects Against Bacterial Infection
Kim, B.-H., Shenoy, A. R., Kumar, P., Das, R., Tiwari, S., & MacMicking, J. D. (2011) · Science · doi:10.1126/science.1201711 · Cited by 494 · see citing works
Self-citationMycobacterium tuberculosis and the Macrophage: Maintaining a Balance
Pieters, J. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.05.006 · Cited by 498 · see citing works
“…on the induction of the immunity-related GTPase (IRG) members that are upregulated following interferon-g treatment, promoting lysosomal delivery (Feng et al., 2004; MacMicking et al., 2003, MacMicking, 2005; Martens and Howard, 2006), possibly via the autophagosomal pathway (Singh et al., 2006).”
BackgroundKhader, S. A., Pearl, J. E., Sakamoto, K., Gilmartin, L., Bell, G. K., Jelley‐Gibbs, D. M., Ghilardi, N., deSauvage, F., & Cooper, A. M. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.2.788 · Cited by 477 · see citing works
“LRG-47 gene (29) (a member of the 47-kDa GTPase family involved in maturation of phagosomes), were both induced in the lungs upon infection.”
BackgroundMycobacterial survival strategies in the phagosome: defence against host stresses
Ehrt, S., & Schnappinger, D. (2009) · Cellular Microbiology · doi:10.1111/j.1462-5822.2009.01335.x · Cited by 448 · see citing works
“Mycobacterium tuberculosis (Mtb) is one of the most prevalent human pathogens that has evolved to prevent the maturation of phagosomes into phagolysosomes (Armstrong and Hart, 1971; Sturgill-Koszycki et al., 1994; MacMicking et al., 2003).”
BackgroundInfluentialThe phagosome: compartment with a license to kill
Haas, A. (2007) · Traffic · doi:10.1111/j.1600-0854.2006.00531.x · Cited by 450 · see citing works
CELL BIOLOGY OF MYCOBACTERIUM TUBERCULOSIS PHAGOSOME
Vergne, I., Chua, J., Singh, S., & Deretic, V. P. (2004) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.20.010403.114015 · Cited by 440 · see citing works
Regulation of antigen presentation by Mycobacterium tuberculosis: a role for Toll-like receptors
Harding, C. V., & Boom, W. H. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2321 · Cited by 435 · see citing works
Tuberculosis Pathogenesis and Immunity
Philips, J. A., & Ernst, J. (2011) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-011811-132458 · Cited by 415 · see citing works
Martineau, A. R., Wilkinson, K. A., Newton, S. M., Floto, R. A., Norman, A. W., Skolimowska, K., Davidson, R. N., Sørensen, O. E., Kampmann, B., Griffiths, C. J., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.11.7190 · Cited by 410 · see citing works
The Immune Escape Mechanisms of Mycobacterium Tuberculosis
Zhai, W., Wu, F., Zhang, Y., Fu, Y., & Liu, Z. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020340 · Cited by 396 · see citing works
Harris, J. (2011) · Cytokine · doi:10.1016/j.cyto.2011.08.022 · Cited by 392 · see citing works
“tuberculosis [20].”
Regulation of neutrophils by interferon-γ limits lung inflammation during tuberculosis infection
Nandi, B., & Behar, S. M. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20110919 · Cited by 373 · see citing works
“IFN- is also an essential component of the human immune response to tuberculosis, although its mechanism of action may differ from that defined in mice (Jouanguy et al., 1996, 1997; MacMicking et al., 1997, 2003; Madariaga et al., 1998).”
BackgroundA membrane protein preserves intrabacterial pH in intraphagosomal Mycobacterium tuberculosis
Vandal, O. H., Pierini, L. M., Schnappinger, D., Nathan, C. F., & Ehrt, S. (2008) · Nature Medicine · doi:10.1038/nm.1795 · Cited by 368 · see citing works
Interplay between mycobacteria and host signalling pathways
Koul, A., Herget, T., Klebl, B., & Ullrich, A. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro840 · Cited by 360 · see citing works
“A recent study indicates that IFN-γ also hinders the replication of mycobacteria by inducing the expression of a GTPase, LRG-47, which promotes phagosomal maturatio”
BackgroundMycobacterium tuberculosis and the environment within the phagosome
Rohde, K. H., Yates, R. M., Purdy, G. E., & Russell, D. G. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00547.x · Cited by 361 · see citing works
Persistent bacterial infections, antibiotic tolerance, and the oxidative stress response
Grant, S. S., & Hung, D. T. (2013) · Virulence · doi:10.4161/viru.23987 · Cited by 362 · see citing works
Autophagy in immunity and cell‐autonomous defense against intracellular microbes
Deretic, V. P. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00995.x · Cited by 363 · see citing works
Muñoz‐Elías, E. J., Upton, A. M., Cherian, J., & McKinney, J. D. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05155.x · Cited by 360 · see citing works
“Male and female C57BL/6 mice age 5–8 weeks (Jackson Laboratories) were infected by the aerosol route with ∼100 cfu using a custom-built aerosol exposure chamber (University of Wisconsin, Madison), as described (MacMicking et al., 2003).”
MethodSelf-citationDisruption of Toxoplasma gondii Parasitophorous Vacuoles by the Mouse p47-Resistance GTPases
Martens, S., Parvanova, I., Zerrahn, J., Griffiths, G. W., Schell, G., Reichmann, G., & Howard, J. C. (2005) · PLoS Pathogens · doi:10.1371/journal.ppat.0010024 · Cited by 356 · see citing works
“Furthermore the individual p47 GTPases are non-equivalent against different pathogens [24–27,44] suggesting a complex relationship between individual members of the p47 family.”
BackgroundInfluentialThe role of cytokines in the initiation, expansion, and control of cellular immunity to tuberculosis
Cooper, A. M., & Khader, S. A. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00702.x · Cited by 353 · see citing works
“Similarly, mice lacking the mediators of antimycobacterial macrophage functions, such as expression of inducible nitric oxide synthase (16) or LRG-47 (17), are unable to control bacterial growth.”
BackgroundKumar, D., Nath, L., Kamal, M. A., Varshney, A., Jain, A., Singh, S., & Rao, K. V. S. (2010) · Cell · doi:10.1016/j.cell.2010.02.012 · Cited by 345 · see citing works
“Although the antimicrobial properties of IFN-g also derive in part from its ability to stimulate autophagy in host cells (MacMicking et al., 2003; Singh et al., 2006), Mtb-infected human macrophages are desensitized to activation by this cytokine (Ting et al., 1999).”
BackgroundNg, V. H., Cox, J. S., Sousa, A. O., MacMicking, J. D., & McKinney, J. D. (2004) · Molecular Microbiology · doi:10.1111/j.1365-2958.2004.04078.x · Cited by 339 · see citing works
“…no direct evidence in support of this model in MTB, it has been shown that the intracellular trafficking and maturation of mycobacterium-containing phagosomes are dramatically altered by cytokine activation of infected macrophages (Schaible et al., 1998; Via et al., 1998; MacMicking et al., 2003).”
BackgroundSelf-citationTeitelbaum, D. H., & Coran, A. G. (2006) · CRC Press eBooks · doi:10.1201/b13237-67 · Cited by 341 · see citing works
Life and death in the granuloma: immunopathology of tuberculosis
Saunders, B. M., & Britton, W. J. (2007) · Immunology and Cell Biology · doi:10.1038/sj.icb.7100027 · Cited by 336 · see citing works
Fremond, C., Togbe, D., Doz, E., Rose, S., Vasseur, V., Maillet, I., Jacobs, M., Ryffel, B., & Quesniaux, V. F. J. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.2.1178 · Cited by 339 · see citing works
“Although IFN- -iNOS2 is considered a principal effector mechanism in MTB control, other pathways exist such as the p47 GTP family member, LRG-47, that acts independently of iNOS to protect against MTB infection (52).”
BackgroundInterferon-induced guanylate-binding proteins: Guardians of host defense in health and disease
Tretina, K., Park, E., Mamińska, A., & MacMicking, J. D. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20182031 · Cited by 323 · see citing works
“Such findings fit with the discovery made at The Rockefeller University nearly a decade earlier that IFN-induced GTPases can directly target the bacterial niche, for example, against M. tuberculosis (MacMicking et al., 2003).”
ResultSelf-citationAlonso, S., Pethe, K., Russell, D. G., & Purdy, G. E. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700036104 · Cited by 318 · see citing works
Andrade, R. M., Wessendarp, M., Gubbels, M., Striepen, B., & Subauste, C. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28796 · Cited by 318 · see citing works
“An association between IFN-γ and phagolysosomal fusion has been observed (9, 10).”
BackgroundIn search of a new paradigm for protective immunity to TB
Nunes-Alves, C., Booty, M. G., Carpenter, S. M., Jayaraman, P., Rothchild, A. C., & Behar, S. M. (2014) · Nature Reviews Microbiology · doi:10.1038/nrmicro3230 · Cited by 307 · see citing works
Lapaquette, P., Glasser, A.-L., Huett, A. S., Xavier, R. J., & Darfeuille–Michaud, A. (2009) · Cellular Microbiology · doi:10.1111/j.1462-5822.2009.01381.x · Cited by 312 · see citing works
“In accordance, defective bacterial killing in LRG-47-/- (a murine ortholog of IRGM) macrophages due to impaired maturation of bacteria-containing phagosomes was reported (MacMicking et al., 2003).”
BackgroundImmunology of Mycobacterium tuberculosis Infections
Sia, J. K., & Rengarajan, J. (2019) · Microbiology Spectrum · doi:10.1128/microbiolspec.gpp3-0022-2018 · Cited by 321 · see citing works
Deretic, V. P., Singh, S., Master, S. S., Harris, J., Roberts, E. A., Kyei, G. B., Davis, A., Haro, S. A. D., Naylor, J., Lee, H.-H., et al. (2006) · Cellular Microbiology · doi:10.1111/j.1462-5822.2006.00705.x · Cited by 306 · see citing works
“…to killing of mycobacteria by a trafficking-independent mechanism, but involves an active membrane sorting mechanism dependent on LRG-47, a member of the family of 47 kDa GTPases inducible by interferon-γ (MacMicking et al., 2003) (LRG-47 mode of action will be covered in the context of autophagy).”
BackgroundGene modulation and immunoregulatory roles of Interferonγ
Saha, B., Prasanna, S. J., Subramanian, B. C., & Nandi, D. (2009) · Cytokine · doi:10.1016/j.cyto.2009.11.021 · Cited by 300 · see citing works
Bekpen, C., Hunn, J. P., Rohde, C., Parvanova, I., Guethlein, L., Dunn, D. M., Glowalla, E., Leptin, M., & Howard, J. C. (2005) · Genome biology · doi:10.1186/gb-2005-6-11-r92 · Cited by 294 · see citing works
“In contrast, there is evidence that LRG-47 is involved in accelerated acidification of the phagocytic vacuole containing Mycobacterium tuberculosis [8].”
BackgroundInfluentialBancerek, J., Poss, Z. C., Steinparzer, I., Sedlyarov, V., Pfaffenwimmer, T., Mikulic, I., Dölken, L., Strobl, B., Müller, M., Taatjes, D. J., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.10.017 · Cited by 297 · see citing works
“Primary Irf1, Wars (also known as Ifp-53), and Ifi47 are each regulated by binding of the STAT1 homodimer to the IFN-g-activated sequence (GAS) in the promoter (MacMicking et al., 2003; Pine et al., 1994; Strehlow et al., 1993).”
IFN-Inducible GTPases in Host Cell Defense
Kim, B.-H., Shenoy, A. R., Kumar, P., Bradfield, C. J., & MacMicking, J. D. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.09.007 · Cited by 278 · see citing works
Self-citationTimm, J., Post, F. A., Bekker, L., Walther, G. B., Wainwright, H., Manganelli, R., Chan, W.-T., Tsenova, L., Gold, B., Smith, I., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436197100 · Cited by 278 · see citing works
Self-citationHölscher, C., Hölscher, A., Rückerl, D., Yoshimoto, T., Yoshida, H., Mak, T. W., Saris, C. J. M., & Ehlers, S. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.6.3534 · Cited by 279 · see citing works
“In addition, the IFN- -dependent GTPase LRG-47 efficiently contributes to the intracellular elimination of mycobacteria by activated macrophages (43).”
BackgroundAcid Resistance inMycobacterium tuberculosis
Vandal, O. H., Nathan, C., & Ehrt, S. (2009) · Journal of Bacteriology · doi:10.1128/jb.00305-09 · Cited by 261 · see citing works
Maartens, G., & Wilkinson, R. J. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61262-8 · Cited by 260 · see citing works
p47 GTPases: regulators of immunity to intracellular pathogens
Taylor, G. A., Feng, C. G., & Sher, A. (2004) · Nature reviews. Immunology · doi:10.1038/nri1270 · Cited by 252 · see citing works
Self-citationLatent Tuberculosis Infection: Myths, Models, and Molecular Mechanisms
Dutta, N. K., & Karakousis, P. C. (2014) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00010-14 · Cited by 248 · see citing works
Desvignes, L., & Ernst, J. (2009) · Immunity · doi:10.1016/j.immuni.2009.10.007 · Cited by 239 · see citing works
Autophagy in Innate and Adaptive Immunity
Xu, Y., & Eissa, N. T. (2010) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200909-103js · Cited by 242 · see citing works
HIF-1α Is an Essential Mediator of IFN-γ–Dependent Immunity to Mycobacterium tuberculosis
Braverman, J., Sogi, K. M., Benjamin, D. I., Nomura, D. K., & Stanley, S. A. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600266 · Cited by 233 · see citing works
Chlamydial IFN-γ immune evasion is linked to host infection tropism
Nelson, D. E., Virok, D. P., Wood, H., Roshick, C., Johnson, R. M., Whitmire, W. M., Crane, D. D., Steele‐Mortimer, O., Kari, L., McClarty, G. A., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504198102 · Cited by 227 · see citing works
Intemann, C. D., Thye, T., Niemann, S., Browne, E. N. L., Chinbuah, M. A., Enimil, A. K., Gyapong, J. O., Osei, I., Owusu‐Dabo, E., Helm, S., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000577 · Cited by 226 · see citing works
“The fact that IRGM is not inducible by IFN-c as are Irg genes in mice [4,7,26] but initiates successfully autophagy as does IFN-c, argues for additional resistance mechanisms in individuals carrying the IRGM 2261T variant homozygously, independent of other Th1-mediated immune responses.”
BackgroundReplication Dynamics of Mycobacterium tuberculosis in Chronically Infected Mice
Muñoz-Elías, E., Timm, J., Botha, T., Chan, W.-T., Gomez, J. E., & Mckinney, J. (2005) · Infection and Immunity · doi:10.1128/iai.73.1.546-551.2005 · Cited by 247 · see citing works
Self-citationHost Innate Immune Response to Mycobacterium tuberculosis
Bhatt, K., & Salgame, P. R. (2007) · Journal of Clinical Immunology · doi:10.1007/s10875-007-9084-0 · Cited by 220 · see citing works
IFN-inducible GTPases and immunity to intracellular pathogens
MacMicking, J. D. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.08.010 · Cited by 221 · see citing works
Self-citationKnight, M., Braverman, J., Asfaha, K., Gronert, K., & Stanley, S. A. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1006874 · Cited by 219 · see citing works
Identification of a copper-binding metallothionein in pathogenic mycobacteria
Gold, B., Deng, H., Bryk, R., Vargas, D., Eliezer, D., Roberts, J., Jiang, X., & Nathan, C. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.109 · Cited by 217 · see citing works
A wearable haemodialysis device for patients with end-stage renal failure: a pilot study
Davenport, A., Gura, V., Ronco, C., Beizai, M., Ezon, C., & Rambod, E. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61864-9 · Cited by 217 · see citing works
Progress in tuberculosis vaccine development and host-directed therapies—a state of the art review
Kaufmann, S. H. E., Lange, C. G., Rao, M., Balaji, K. N., Lotze, M. T., Schito, M. L., Zumla, A. I., & Maeurer, M. J. (2014) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(14)70033-5 · Cited by 217 · see citing works
Nuclear receptor ERRα and coactivator PGC-1β are effectors of IFN-γ-induced host defensePreprint
Sonoda, J., Laganière, J., Mehl, I. R., Barish, G. D., Chong, L.-W., Li, X., Scheffler, I. E., Mock, D. C., Bataille, A. R., Robert, F., et al. (2007) · Genes & Development · doi:10.1101/gad.1553007 · Cited by 217 · see citing works
“1995) and GTP-binding protein LRG-47 (MacMicking et al. 2003; Gutierrez et al. 2004).”
BackgroundInterferon-Inducible GTPases in Host Resistance, Inflammation and Disease
Pilla-Moffett, D. M., Barber, M. F., Taylor, G. A., & Coers, J. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.04.032 · Cited by 216 · see citing works
Self-citationJayaraman, P., Sada‐Ovalle, I., Nishimura, T., Anderson, A. C., Kuchroo, V. K., Remold, H. G., & Behar, S. M. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202688 · Cited by 217 · see citing works
The immunology of tuberculosis: From bench to bedside
Dheda, K. U. J., Schwander, S., Zhu, B., van Zyl-Smit, R. N., & Zhang, Y. (2010) · Respirology · doi:10.1111/j.1440-1843.2010.01739.x · Cited by 212 · see citing works
Autophagy in innate and adaptive immunity.
Deretic, V. (2005) · Trends in immunology · doi:10.1016/j.it.2005.08.003 · Cited by 89 · see citing works
Autophagy as an immune defense mechanism.
Deretic, V. (2006) · Current Opinion in Immunology · doi:10.1016/j.coi.2006.05.019 · Cited by 208 · see citing works
The Trojan horse: survival tactics of pathogenic mycobacteria in macrophages
Nguyen, L., & Pieters, J. (2005) · Trends in Cell Biology · doi:10.1016/j.tcb.2005.03.009 · Cited by 204 · see citing works
Coordinated loading of IRG resistance GTPases on to the Toxoplasma gondii parasitophorous vacuole
Khaminets, A., Hunn, J. P., Könen‐Waisman, S., Zhao, Y. O., Preukschat, D., Coers, J., Boyle, J. P., Ong, Y.-C., Boothroyd, J. C., Reichmann, G., et al. (2010) · Cellular Microbiology · doi:10.1111/j.1462-5822.2010.01443.x · Cited by 204 · see citing works
“Because Irgm1 has been shown to relocate to phagocytic cups and phagosomes during particle uptake (MacMicking et al., 2003; Martens et al., 2004) it has been proposed that this IRG protein can implement a direct cell-autonomous attack on phagocytosed pathogens (MacMicking et al., 2003).”
BackgroundThe Innate Immune Response to Mycobacterium tuberculosis Infection
Ravesloot-Chávez, M. M., Dis, E. S. V., & Stanley, S. A. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-093019-010426 · Cited by 208 · see citing works
Salgame, P. R. (2005) · Current Opinion in Immunology · doi:10.1016/j.coi.2005.06.006 · Cited by 202 · see citing works
Tim3 binding to galectin-9 stimulates antimicrobial immunity
Jayaraman, P., Sada‐Ovalle, I., Beladi, S., Anderson, A. C., Dardalhon, V., Hotta, C., Kuchroo, V. K., & Behar, S. M. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20100687 · Cited by 198 · see citing works
“To definitively rule out the involvement of IFN- and iNOS in Tim3–Gal9–mediated Mtb killing, IFN-R/ and iNOS/ macrophages were infected with Mtb and treated with Tim3-Ig.”
BackgroundInfluentialMycobacterium tuberculosis Wears What It Eats
Russell, D. G., VanderVen, B. C., Lee, W., Abramovitch, R. B., Kim, M., Homolka, S., Niemann, S., & Rohde, K. H. (2010) · Cell Host & Microbe · doi:10.1016/j.chom.2010.06.002 · Cited by 194 · see citing works
“Activation of the host macrophage by either TLR agonists or IFN-γ leads to alterations in the Mtb-containing phagosome that impact negatively on the bacterium’s capacity to replicate and/or survive (MacMicking et al., 2003; Schaible et al., 1998; Via et al., 1998).”
BackgroundMcNab, F. W., Ewbank, J., Howes, A., Moreira-Teixeira, L., Մարտիրոսյան, Ա., Ghilardi, N., Saraiva, M., & O’Garra, A. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401088 · Cited by 198 · see citing works
“cellular bacterial growth through induction of antimicrobial effectors such as iNOS (5, 6, 12, 14).”
BackgroundBaldwin, C. L., & Goenka, R. (2006) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.v26.i5.30 · Cited by 191 · see citing works
The macrophage marches on its phagosome: dynamic assays of phagosome function
Russell, D. G., VanderVen, B. C., Glennie, S. J., Mwandumba, H. C., & Heyderman, R. S. (2009) · Nature reviews. Immunology · doi:10.1038/nri2591 · Cited by 188 · see citing works
Kahnert, A., Seiler, P. J., Stein, M., Bandermann, S., Hahnke, K., Mollenkopf, H., & Kaufmann, S. H. E. (2006) · European Journal of Immunology · doi:10.1002/eji.200535496 · Cited by 187 · see citing works
NLRP4 Negatively Regulates Autophagic Processes through an Association with Beclin1
Jounai, N., Kobiyama, K., Shiina, M., Ogata, K., Ishii, K. J., & Takeshita, F. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1001654 · Cited by 186 · see citing works
Selective Killing of Nonreplicating Mycobacteria
Bryk, R., Gold, B., Venugopal, A., Singh, J., Samy, R. D., Pupek, K., Cao, H., Popescu, C., Gurney, M., Hotha, S., et al. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.02.003 · Cited by 184 · see citing works
“The following conditions are thought to exist in the Mtb-containing phagosome in immunocompetent hosts: a pH of 4.5 (MacMicking et al., 2003); NO diffusing from the cytosol and/or locally generated after acidification of its auto-oxidation product, nitrite (Nathan and Ehrt, 2004); lack of leucine…”
BackgroundMethodInfluentialTuberculosis and the art of macrophage manipulation
Upadhyay, S., Mittal, E., & Philips, J. A. (2018) · Pathogens and Disease · doi:10.1093/femspd/fty037 · Cited by 178 · see citing works
Bougnères, L., Helft, J., Tiwari, S., Vargas, P., Chang, B. H.-J., Chan, L., Campisi, L., Lauvau, G. S., Hugues, S., Kumar, P., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.022 · Cited by 179 · see citing works
“Previous studies have shown that the expression of Igtp is uniformly low in various cell types and further increased by IFN exposure (MacMicking et al., 2003; Taylor et al., 2000, 1996).”
BackgroundSelf-citationBagshaw, R. D., Mahuran, D. J., & Callahan, J. W. (2004) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m400128-mcp200 · Cited by 175 · see citing works
Mycobacterium tuberculosis-Specific CD8+ T Cells and Their Role in Immunity
Woodworth, J. S., & Behar, S. M. (2006) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.v26.i4.30 · Cited by 175 · see citing works
Autophagy and pattern recognition receptors in innate immunity
Delgado, M. A., Singh, S., Haro, S. A. D., Master, S. S., Ponpuak, M., Dinkins, C., Ornatowski, W., Vergne, I., & Deretic, V. P. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00725.x · Cited by 174 · see citing works
Interferon- γ and infectious diseases: Lessons and prospects
Casanova, J., MacMicking, J. D., & Nathan, C. (2024) · Science · doi:10.1126/science.adl2016 · Cited by 179 · see citing works
Self-citation
- Authors
- MacMicking, J. D., Taylor, G. A., & McKinney, J. D.
- Affiliations
- Duke University (US)
- Corresponding author
- MacMicking, John D.
- Venue
- Science
- Published
- 2003-10-24
- Volume
- 302
- Issue
- 5645
- Pages
- 654-659
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1989883893
- Cited by
- 685
- References
- 31
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 16 · 2023: 21 · 2022: 15 · 2021: 27 · 2020: 23 · 2019: 26 · 2018: 27 · 2017: 21 · 2016: 21 · 2015: 34 · 2014: 31 · 2013: 44 · 2012: 44
- FWCI
- 19.81
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- U.S. Public Health Service (R01 A1051702)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- tuberculosis, interferon-gamma, Mycobacterium tuberculosis, nitric oxide synthase 2, intracellular pathogen clearance, vacuolar trafficking, host immunity
- MeSH terms
- Animals, Cells, Cultured, Disease Susceptibility, Female, Hydrogen-Ion Concentration, Immunity, Innate, Interferon-gamma, Macrophage Activation, Macrophages, Male, Mice, Inbred C57BL, Mutation, Mycobacterium tuberculosis, Phagosomes, Tuberculosis, Signal Transduction, Macrophages, Alveolar, Nitric Oxide Synthase, GTP-Binding Proteins, Computational Biology, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, GTP Phosphohydrolases, Mice, Nitric Oxide Synthase Type II
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