CD40-TRAF6 and Autophagy-Dependant Anti-Microbial Activity in Macrophages

Subauste, Carlos S.; Andrade, Rosa; Wessendarp, Matthew

doi:10.4161/auto.3717

Cited by 67 publications

(91 citation statements)

References 27 publications

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“…CD40 induces killing of T. gondii through vacuolelysosome fusion because pharmacologic inhibition and genetic manipulation of molecules key for vesicular trafficking and lysosomal degradation [lysosomal enzymes, vacuolar ATPase, class III phosphatidylinositol 3-kinase (PI3K) or hVps34, Rab7] abrogate killing of T. gondii induced by CD40 (Andrade et al 2006). These studies uncovered a new paradigm where interaction between CD154 on T cells and CD40 expressed on macrophages leads to killing of an intracellular pathogen via the induction of vacuole-lysosomal fusion (Andrade et al 2006, Subauste et al 2007a). Vacuole-lysosome fusion induced by CD40 likely contributes to host protection because CD40 stimulation in vivo induces macrophage toxoplasmacidal activity and reduces the parasite load .…”

Section: Cd40 Transforms the Parasitophorous Vacuole Into A Compartmementioning

confidence: 98%

“…CD40 has two binding sites that directly recruit TRAF2 and TRAF3 and a binding site that directly recruits TRAF6 (Ishida et al 1996, Pullen et al 1998, Lu et al 2003. The TRAF6 binding site plays a dual role in the autophagic killing of T. gondii: it enhances autocrine production of TNF-α (Mukundan et al 2005) and TRAF6 signaling downstream of CD40 synergizes with TNF-α to activate autophagy (Subauste et al 2007a). As a result, autophagosomes are recruited around the parasitophorous vacuole and this is followed by Rab7-dependent fusion with late endosomes-lysosomes and killing of T. gondii (Andrade 2005b(Andrade , 2006 (Figure).…”

Section: Cd40 Induces Vacuole -Lysosomal Fusion and Toxoplasmacidal Amentioning

confidence: 99%

“…CD40 causes fusion of parasite-containing vacuoles with late endosomes-lysosomes (Andrade et al 2006, Subauste et al 2007a. A critical question was whether parasitophorous vacuoles, which by definition have been considered non-fusogeneic, fused with late endosomeslysosomes.…”

Section: Cd40 Transforms the Parasitophorous Vacuole Into A Compartmementioning

confidence: 99%

“…Recent studies revealed that CD40 signals through adapter proteins to trigger autophagy (Subauste et al 2007a). TNF Receptor Associated Factors (TRAF) are adapter proteins recruited to the intra-cytoplasmic tail of CD40 (Bishop et al 2007).…”

Section: Cd40 Induces Vacuole -Lysosomal Fusion and Toxoplasmacidal Amentioning

confidence: 99%

“…This question is not only relevant to T. gondii but also to the large number of pathogens that survive by avoiding phago-lysosomal fusion. We recently demonstrated that this is achieved through CD40 stimulation (Andrade et al 2006, Subauste et al 2007a …”

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CD40, autophagy and Toxoplasma gondii

Subauste

2009

Mem. Inst. Oswaldo Cruz

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Section: Cd40 Transforms the Parasitophorous Vacuole Into A Compartmementioning

confidence: 98%

Section: Cd40 Induces Vacuole -Lysosomal Fusion and Toxoplasmacidal Amentioning

confidence: 99%

Section: Cd40 Transforms the Parasitophorous Vacuole Into A Compartmementioning

confidence: 99%

Section: Cd40 Induces Vacuole -Lysosomal Fusion and Toxoplasmacidal Amentioning

confidence: 99%

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confidence: 99%

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CD40, autophagy and Toxoplasma gondii

Subauste

2009

Mem. Inst. Oswaldo Cruz

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Autophagy

Colombo¹,

Simon²

2009

Encyclopedia of Life Sciences

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Autophagy is a conserved proteolytic mechanism that degrades cytoplasmic material including cell organelles. Although the importance of autophagy for cell homeostasis and survival has long been appreciated, our understanding of how autophagy is regulated at a molecular level just recently evolved. The importance of autophagy for the quality control of proteins is underscored by the fact that many neurodegenerative and myodegenerative diseases are characterized by an increased but still insufficient autophagic activity. Similarly, if the cellular stress, leading to deoxyribonucleic acid (DNA) damage, mitochondrial damage and/or damaged proteins, does not result in sufficient autophagic repair mechanisms, cells seem to be prone to transform into tumour cells. Therefore, autophagy has multiple roles to play in the causation and prevention of human diseases. Key concepts: Autophagy is a cellular stress response induced to ensure cell survival, but excess autophagy may lead to cell death. The kinases TOR (target of rapamycin) and PI3K (phosphatidyl inositol 3 kinase) are two essential components of the autophagy molecular machinery. The family of genes or proteins called Atg (for a u t opha g y related) comprises the core of the molecular machinery of autophagy. Upon autophagy induction the enwrapped cytoplasmic components and organelles are recycled by degradation in the autolysosome. Autophagy can be dysregulated and may contribute to many pathologic processes.

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Apicomplexa: Toxoplasma gondii

Wilson¹

2012

Immunity to Parasitic Infection

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CD40-TRAF6 and Autophagy-Dependant Anti-Microbial Activity in Macrophages

Cited by 67 publications

References 27 publications

CD40, autophagy and Toxoplasma gondii

CD40, autophagy and Toxoplasma gondii

Autophagy

Apicomplexa: Toxoplasma gondii

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