Construction of chimeric phagosomes that shelter Mycobacterium avium and Coxiella burnetii (phase II) in doubly infected mouse macrophages: an ultrastructural study

Chastellier, Chantal de; Thibon, M; Rabinovitch, M.

doi:10.1016/s0171-9335(99)80024-7

Cited by 29 publications

(24 citation statements)

References 67 publications

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“…The second characteristic reported for the C. burnetii vacuole is its ability to fuse with different intracellular compartments, including lysosomes. Hence, vacuoles that enclose C. burnetii can become large, contain numerous organisms, and fuse with vacuoles containing Leishmania amazonensis or M. avium (25,26). The conclusions of these studies are limited by their use of avirulent organisms and cells in which C. burnetii replication was independent of bacterial virulence.…”

Section: Discussionmentioning

confidence: 99%

Coxiella burnetiiSurvival in THP-1 Monocytes Involves the Impairment of Phagosome Maturation: IFN-γ Mediates its Restoration and Bacterial Killing

Ghigo

Capo

Tung

et al. 2002

The Journal of Immunology

136

143

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The subversion of microbicidal functions of macrophages by intracellular pathogens is critical for their survival and pathogenicity. The replication of Coxiella burnetii, the agent of Q fever, in acidic phagolysosomes of nonphagocytic cells has been considered as a paradigm of intracellular life of bacteria. We show in this study that C. burnetii survival in THP-1 monocytes was not related to phagosomal pH because bacterial vacuoles were acidic independently of C. burnetii virulence. In contrast, virulent C. burnetii escapes killing in resting THP-1 cells by preventing phagosome maturation. Indeed, C. burnetii vacuoles did not fuse with lysosomes because they were devoid of cathepsin D, and did not accumulate lysosomal trackers; the acquisition of markers of late endosomes and late endosomes-early lysosomes was conserved. In contrast, avirulent variants of C. burnetii were eliminated by monocytes and their vacuoles accumulated late endosomal and lysosomal markers. The fate of virulent C. burnetii in THP-1 monocytes depends on cell activation. Monocyte activation by IFN-γ restored C. burnetii killing and phagosome maturation as assessed by colocalization of C. burnetii with active cathepsin D. In addition, when IFN-γ was added before cell infection, it was able to stimulate C. burnetii killing but it also induced vacuolar alkalinization. These findings suggest that IFN-γ mediates C. burnetii killing via two distinct mechanisms, phagosome maturation, and phagosome alkalinization. Thus, the tuning of vacuole biogenesis is likely a key part of C. burnetii survival and the pathophysiology of Q fever.

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Section: Discussionmentioning

confidence: 99%

Coxiella burnetiiSurvival in THP-1 Monocytes Involves the Impairment of Phagosome Maturation: IFN-γ Mediates its Restoration and Bacterial Killing

Ghigo

Capo

Tung

et al. 2002

The Journal of Immunology

136

143

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“…These data demonstrate that bacterial protein synthesis, but not replication, is required for the formation of the spacious RCV. In addition, unlike lysosomes, Coxiella-containing vacuoles (CVs) undergo both homo-and heterotypic fusion with a large variety of different compartments, including pinocytic vesicles containing thorium dioxide, horseradish peroxidase, or ferritin (1,11), as well as phagosomes containing beads (198), yeast (198), zymosan (198), Mycobacterium species (45,74), or Leishmania amazonensis (199). Finally, as described below, C. burnetii actively promotes interactions with the autophagy pathway (17,81,154), which is thought to delay fusion with lysosomes.…”

Section: Coxiella Burnetiimentioning

confidence: 99%

Manipulation of Rab GTPase Function by Intracellular Bacterial Pathogens

Brumell

Scidmore

2007

Microbiol Mol Biol Rev

189

201

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SUMMARY Intracellular bacterial pathogens have evolved highly specialized mechanisms to enter and survive within their eukaryotic hosts. In order to do this, bacterial pathogens need to avoid host cell degradation and obtain nutrients and biosynthetic precursors, as well as evade detection by the host immune system. To create an intracellular niche that is favorable for replication, some intracellular pathogens inhibit the maturation of the phagosome or exit the endocytic pathway by modifying the identity of their phagosome through the exploitation of host cell trafficking pathways. In eukaryotic cells, organelle identity is determined, in part, by the composition of active Rab GTPases on the membranes of each organelle. This review describes our current understanding of how selected bacterial pathogens regulate host trafficking pathways by the selective inclusion or retention of Rab GTPases on membranes of the vacuoles that they occupy in host cells during infection.

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Section: Introductionmentioning

confidence: 99%

“…Thus when treated with c-interferon (IFNc) plus lipopolysaccharide (LPS) macrophages show increased phagosome acidification (Schaible et al, 1998). Acidification in itself does not explain the anti-mycobacterial activity of macrophages (de Chastellier et al, 1999;Gomes et al, 1999b) and more likely reflects an enhancement in 3Present address: Instituto Gulbenkian de Ciê ncia, Oeiras, Portugal.Abbreviations: FACS, fluorescence-activated cell sorting; 5,59,6,19,3, the maturation of the phagosome (Schaible et al, 1998). This would promote contact of the pathogen with a lower pH, a reducing environment and acid hydrolases as well as conditions favouring the generation of oxidative radicals (Schaible et al, 1998).…”

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confidence: 99%

Induction of Mycobacterium avium growth restriction and inhibition of phagosome–endosome interactions during macrophage activation and apoptosis induction by picolinic acid plus IFNγ

Pais¹,

Appelberg²

2004

Microbiology

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Treatment of mouse macrophages with picolinic acid (PA) and c-interferon (IFNc) led to the restriction of Mycobacterium avium proliferation concomitant with the sequential acquisition of metabolic changes typical of apoptosis, mitochondrial depolarization, annexin V staining and caspase activation, over a period of up to 5 days. However, triggering of cell death by ATP, staurosporine or H 2 O 2 failed to affect mycobacterial viability. In contrast to untreated macrophages where extensive interactions between phagosomes and endosomes were observed, phagosomes from treated macrophages lost the ability to acquire endosomal dextran. N-Acetylcysteine was able to revert both the anti-mycobacterial activity of treated macrophages as well as the block in phagosome-endosome interactions. The treatment, however, induced only a minor increase in the acquisition of lysosomal markers, namely Lamp-1, and did not increase to any great extent the acidification of the phagosomes. These data thus suggest that the anti-mycobacterial activity of PA and IFNc depends on the interruption of intracellular vesicular trafficking, namely the blocking of acquisition of endosomal material by the microbe. INTRODUCTIONMycobacterium avium is an opportunistic pathogen that infects patients suffering from local or systemic deficiencies of the immune system (Falkinham, 1996). Resistance to infection is dependent on both innate mechanisms and acquired immunity through the development of antigenspecific CD4 + T cells (Appelberg, 1994;Holland, 1996). M. avium replicates inside the macrophage and is particularly resistant to the oxidative antimicrobial mechanisms of this phagocyte (Gomes & Appelberg, 2002;Gomes et al., 1999a). Like other pathogenic mycobacteria, M. avium has evolved survival strategies that interfere with the normal intracellular trafficking of vesicular compartments. After being internalized by macrophages, mycobacteria inhibit the fusion of the vacuole they inhabit with lysosomes, thus blocking maturation of the phagosomes into phagolysosomes and proliferating in vacuoles with early endosomal characteristics (Armstrong & d'Arcy-Hart, 1971;Clemens & Horwitz, 1995;Frehel et al., 1986;Russell et al., 1997). Several mechanisms associated with this inhibition have been described, such as reduced phagosomal acidification (Crowle et al., 1991;Sturgill-Koszycki et al., 1994;de Chastellier et al., 1995) due to exclusion of the vacuolar H + -ATPase , altered signalling pathways (Malik et al., 2001;Fratti et al., 2003), interference with the recycling of Rab proteins (Via et al., 1997), retention of the actin-binding coronin/TACO protein (Ferrari et al., 1999; see also Schuller et al., 2001, for a critical reappraisal of this issue), disorganization of the actin filament network (Guérin & de Chastellier, 2000) and tight apposition of the membrane vacuole to the surface of the pathogen, leading to altered exchange of fusion factors (de Chastellier & Thilo, 1997). However, mycobacterial phagosomes keep their ability to interact extensively wi...

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Construction of chimeric phagosomes that shelter Mycobacterium avium and Coxiella burnetii (phase II) in doubly infected mouse macrophages: an ultrastructural study

Cited by 29 publications

References 67 publications

Coxiella burnetiiSurvival in THP-1 Monocytes Involves the Impairment of Phagosome Maturation: IFN-γ Mediates its Restoration and Bacterial Killing

Coxiella burnetiiSurvival in THP-1 Monocytes Involves the Impairment of Phagosome Maturation: IFN-γ Mediates its Restoration and Bacterial Killing

Manipulation of Rab GTPase Function by Intracellular Bacterial Pathogens

Induction of Mycobacterium avium growth restriction and inhibition of phagosome–endosome interactions during macrophage activation and apoptosis induction by picolinic acid plus IFNγ

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