Browsing by Author "Griffiths, Gareth"
Now showing 1 - 10 of 11
Results Per Page
Sort Options
- Anti-inflammatory effects of phosphatidylcholinePublication . Treede, Irina; Braun, Annika; Sparla, Richard; Kuehnel, Mark; Giese, Thomas; Turner, Jerrold R.; Anes, Elsa; Kulaksiz, Hasan; Fuellekrug, Joachim; Stremmel, Wolfgang; Griffiths, Gareth; Ehehalt, RobertWe recently showed that mucus from patients with ulcerative colitis, a chronic inflammatory disorder of the colon, is characterized by a low level of phosphatidylcholine (PC) while clinical studies reveal that therapeutic addition of PC using slow release
- cAMP synthesis and degradation by phagosomes regulate actin assembly and fusion eventsPublication . Kalamidas, Stefanos A.; Kuehnel, Mark P.; Peyron, Pascale; Rybin, Vladimir; Rauch, Susanne; Kotoulas, Othon B.; Houslay, Miles; Hemmings, Brian A.; Gutierrez, Maximiliano G.; Anes, Elsa; Griffiths, GarethWe showed recently that actin assembly by phagosomal membranes facilitates fusion with late endocytic organelles in macrophages. Moreover, lipids that induced phagosomal actin also stimulated this fusion process. In macrophages infected with pathogenic my
- Effects of omega-3 and-6 fatty acids on Mycobacterium tuberculosis in macrophages and in micePublication . Jordao, Luisa; Lengeling, Andreas; Bordat, Yann; Boudou, Frederic; Gicquel, Brigitte; Neyrolles, Olivier; Becker, Pablo D.; Guzman, Carlos A.; Griffiths, Gareth; Anes, ElsaWe recently showed that treatment of macrophages prior to Mycobacterium tuberculosis infection with the pro-inflammatory omega-6 lipid, arachidonic acid (AA) enhanced bacterial killing whereas the anti - inflammatory, omega-3 lipid eicosapentaenoic acid (. - FCT ; FEDER [POCI/BIA-BCM/55327/2004, SFRWBD/14284/2003]. - We thank Cecilia Rodrigues, Maximilliano Gutierrez, Luis Mayorga and Sabrina Marion for their constructive support and discussion. This work was financed by FCT with co-participation of FEDER (POCI/BIA-BCM/55327/2004 and SFRWBD/14284/2003).
- Exosomal Hsp70 induces a pro-inflammatory response to foreign particles including mycobacteriaPublication . Anand, Paras K.; Anand, Ellis; Bleck, Christopher K. E.; Anes, Elsa; Griffiths, GarethBackground: Exosomes are endosome-derived vesicles that are released when multi-vesicular bodies (MVBs) fuse with the plasma membrane. Exosomes released from mycobacteria-infected cells have recently been shown to be pro-inflammatory. A prominent host molecule that is found within these exosomes is Hsp70, a member of the heat-shock family of proteins. Methodology/Principal Findings: We first characterized the exosomes purified from control and mycobacteria-infected cells. We found that relative to uninfected cells, macrophages infected with M. smegmatis and M. avium release more exosomes and the exosomes they released had more Hsp70 on their surface. Both exosomes and exogenous Hsp70 treatment of macrophages led to NF-kB activation and TNFa release in uninfected macrophages; Hsp70 levels were elevated in mycobacteria-infected cells. Macrophage treatment with Hsp70 also led to increase in the phagocytosis and maturation of latex-bead phagosomes. Finally, Hsp70 pre-incubation of M. smegmatis- and M. avium-infected cells led to increased phago-lysosome fusion, as well as more killing of mycobacteria within macrophages. Conclusions/Significance: Our results fit into an emerging concept whereby exosomes-containing Hsp70 are effective inducers of inflammation, also in response to mycobacterial infection.
- Isolation of latex bead and mycobacterial phagosomesPublication . Kühnel, Mark; Anes, Elsa; Griffiths, GarethMethods to isolate mycobacteria containing phagosomes
- Lipids regulate P2X7-receptor-dependent actin assembly by phagosomes via ADP translocation and ATP synthesis in the phagosome lumenPublication . Kuehnel, Mark. P.; Rybin, Vladimir; Anand, Paras K.; Anes, Elsa; Griffiths, GarethLatex bead phagosomes isolated from J774 macrophages polymerize actin. We show here that five lipids phosphatidylinositol-4-phosphate, phosphatidylinositol-(4,5)bisphosphate, sphingosine-1-phosphate (S1P), ceramide-1-phosphate and phosphatidic acid - stim. - Fundacao para a Ciencia e a tecnologia (FCT). - We would like to thank Sabrina Marion and Simi Antony for their technical support. We greatly appreciate the suggestions by Jens Reich and Thomas Dandekar. Thanks also to Christopher Bleck for preparing Fig. 4 and to Luis Mayorga, Sabrina Marion and Maxim
- Modelling phagosomal lipid networks that regulate actin assemblyPublication . Kuehnel, Mark; Mayorga, Luis S.; Dandekar, Thomas; Thakar, Juilee; Schwarz, Roland; Anes, Elsa; Griffiths, Gareth; Reich, JensBackground: When purified phagosomes are incubated in the presence of actin under appropriate conditions, microfilaments start growing from the membrane in a process that is affected by ATP and the lipid composition of the membrane. Isolated phagosomes ar. - DFG [Da 208/7-2, TR34]; BMBF ; Irvington Institute CRI ; FEDER [POCI, PPCDT/BIA- BCM/55327/2004]; Alexander von Humboldt Foundation ; CONICET. - We thank J. Brouwers and B. Helms from Univ. Utrecht, Holland for communicating unpublished data on lipids in LBP phagosomes. This work was generously supported by DFG (Da 208/7-2; TR34), BMBF (Hepatosys, TD and JR; PathogenomikPlus, RS), the Irvington In
- Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the NLRP3/ASC inflammasome.Publication . Mishra, Bibhuti Bhusan; Moura-Alves, Pedro; Sonawane, Avinash; Hacohen, Nir; Griffiths, Gareth; Moita, Luis F.; Anes, ElsaInterleukin-1β (IL-1β) represents one of the most important mediators of inflammation and host responses to infection. Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis, induces IL-1β secretion at the site of infection, but the underlying mechanism(s) are poorly understood. In this work we show that Mtb infection of macrophages stimulates caspase-1 activity and promotes the secretion of IL-1β. This stimulation requires live intracellular bacteria expressing a functional ESX-1 secretion system. ESAT-6, an ESX-1 substrate implicated in membrane damage, is both necessary and sufficient for caspase-1 activation and IL-1β secretion. ESAT-6 promotes the access of other immunostimulatory agents such as AG85 into the macrophage cytosol, indicating that this protein may contribute to caspase-1 activation largely by perturbing host cell membranes. Using a high-throughput shRNA-based screen we found that numerous NOD-like receptors (NLRs) and CARD domain-containing proteins (CARDs) were important for IL-1β secretion upon Mtb infection. Most importantly, NLRP3, ASC and caspase-1 form an infection-inducible inflammasome complex that is essential for IL-1β secretion. In summary, we show that recognition of Mtb infection by the NLRP3 inflammasome requires the activity of the bacterial virulence factor ESAT-6, and the subsequent IL-1β response is regulated by a number of NLR/CARD proteins.
- NF-kappa B activation controls phagolysosome fusion-mediated killing of mycobacteria by macrophagesPublication . Gutierrez, Maximiliano Gabriel; Mishra, Bibhuti B.; Jordao, Luisa; Elliott, Edith; Anes, Elsa; Griffiths, GarethMacrophages can potentially kill all mycobacteria by poorly understood mechanisms. In this study, we explore the role of NF-kappa B in the innate immune response of macrophages against Mycobacterium smegmatis, a nonpathogenic mycobacterium efficiently kil
- On the killing of mycobacteria by macrophagesPublication . Jordao, Luisa; Bleck, Christopher K. E.; Mayorga, Luis; Griffiths, Gareth; Anes, ElsaBoth pathogenic and non-pathogenic mycobacteria are internalized into macrophage phagosomes. Whereas the non-pathogenic types are invariably killed by all macrophages, the pathogens generally survive and grow. Here, we addressed the survival, production o