The ability of Koch’s bacilli to create active disease or a latent infection relay, in part, on the powerful mechanisms it has evolved to parasitize host macrophages and dendritic cells (DCs). While activated macrophages are able to kill intracellular bacteria, and therefore to completely clear Mycobacterium tuberculosis, DCs are enable to eliminate the infection.
We revealed that the killing process of mycobacteria in macrophages is associated with complex membrane trafficking phenomena that accompany phagosome maturation. The goal for the next period is to continue to understand the pro-inflammatory mechanisms by which macrophages kill mycobacteria, and how these mechanisms are regulated.
DCs have developed specific control of endocytic functions in order to allow efficient antigen presentation. They contain lower levels of active lysosomal proteases and impaired phagosome acidification when compared to macrophages. The mild pH of the DCs endocytic pathway assures an efficient processing of pathogen antigens in which cysteine cathepsins and their natural inhibitors cystatins play a crucial role. We propose to elucidate the role of cysteine cathepsins in mycobacterial antigen presentation and/or intracellular killing either in DCs or macrophages.
Further understanding of the molecular mechanisms involved in intracellular killing or survival of mycobacteria will provide a valuable approach to modulate the immune response to tuberculosis.
Elsa Anes
PhD (1998, University of Lisbon)
Assistant Professor, Faculdade de Farmácia, Universidade de Lisboa
Post-doc visitor EMBL, Griffiths Group, Heidelberg, 2000-2005
External group at IMM since 2008
2007/2009 - Identification and manipulation of phagosomal signaling networks to activate killing mechanisms of macrophages infected with mycobacteria, FCT (PPCDT/BIA-BCM/55327/2004).
2009/2011 - Interference of Mycobacterium tuberculosis with the endocytic/ antigen presentation pathways on macrophages and dendritic cells from healthy and immuno-compromised donors, FCT (PIC/IC/82859/2007).
Gareth Griffiths (Oslo Univ., Norway)
Olivier Neyrolles (CNRS, Toulouse, Fr)
Ludovic Tailleux (Inst. Pasteur, Paris, Fr)
Tina Bergant (Jožef Stefan Inst., Ljubljana, Slov)
Carlos Guzman (Helmoholtz Centre for Infection Research, Braunschweig, Ger)
Maximiliano Gutierrez (Helmoholtz Centre for Infection Research, Braunschweig, Ger)
Michael Niederweiss (University of Alabama at Birmingham, USA)
Luis Constantino (iMed, FFUL, Pt)
Luis Moita (IMM, UL, Pt)
Anes E. 2003. “Lípidos da dieta no tratamento da tuberculose.” Medicina & Saúde® 72:15.
Anes E. 2003. “Lípidos da dieta no tratamento da tuberculose”.Suplemento do Jornal Expresso:Saúde Pública® n.º 1, 06 de Março de 2004 – Página 5
Ana Machado, 2003. Público 28/11. Conclusão de equipa da FFUL: Lípidos podem ser uma nova arma no tratamento e prevenção da Tuberculose.
BioWorld Today.2003. How can Dietary lipids some day overcome tuberculosis in animal models, if not people. Sept, 10th,pg9.
Trevor M. D’Souza. Hum-Molgen.2003. A fatty end to pathogenic bacteria. New Ed Kai Garlipp
Terra, Ciência y tecnologia México.2003. Comer carne prevendria tuberculosis. Notimex 8/12/2003
Fuerza Informativa Azteca México.2003. Comer carne prevendria tuberculosis. 12/04/2003
Jorge Rodriguez (ed). Al Dia Cuba. 2003. Dieta rica en determinados lípidos puede ayudar a prevenir la tuberculosis. 15/12/2003
BBC, London. 2003. The fat end of mycobacteria. Intervue to Gareth Griffiths
Madalena Barbosa. 2006. Investigadora Portuguesa lidera projecto. À procura de alternativas para tratar a tuberculose. Medicina & Saúde® 107/38-39
Madalena Barbosa. 2006. Investigadores portugueses procuram alternativas terapeuticas: o papel dos lípidos na luta contra a tuberculose. Jornal Expresso, sup. Saúde Pública, sábado 2 Setembro
Madalena Barbosa. 2006. Investigadores portugueses procuram alternativas terapeuticas: Dieta de lípidos: uma ajuda contra a tuberculose? Jornal Público, sup. Saúde em Dia, sexta-feira, 20 Outubro
2007 Keystone Symposia Award for participatingin the “Tuberculosis: From Lab Research to Field Trials” (C6-2007) (to Bibhuti Bhusan Mishra)
2006 Prémio Câmara Pestana (to Elsa Anes)
2006 Prémio Cotec (Associação Empresarial para a Inovação)/FLAD, (to Elsa Anes)
2005 EMBO Award ASTF 185b-05 (to Elsa Anes)
2000 EMBO Award ASTF9678 (to Elsa Anes)
Kuehnel M, Rybin V, Anand P, Anes E and Gareth Griffiths. 2009. Lipids regulate P2X7 receptor-dependent actin assembly by phagosomes via ADP translocation and ATP synthesis in the phagosome lumen. J Cell Science 122(Pt 4):499-504.
Gutierrez MG, Gonzalez AP, Anes E and Griffiths G. 2009. Role of lipids in killing mycobacteria by macrophages: evidence for NF-kB-dependent and -independent killing induced by different lipids. Cell Microbiol 11(3):406-20.
Simões MF, Valente E, Rodriguez-Gomez MJ, Anes E* and Constantino L*. 2009.
Lipophilic POA amide and ester prodrugs. Stability, activation and activity against M.tuberculosis. Eur. J. Pharm. Sci, doi:10.1016/j.ejps.2009.02.012. * joined corresponding authors.
Jordao L, Lengeling A, Bordat Y, Boudou F, Gicquel G, Neyrolles O, Becker PD, Guzman C, Griffiths G and Anes E. 2008. Effects of omega-3 and -6 fatty acids on Mycobacterium tuberculosis in macrophages and in mice. Microb Infect 10 (12-13):1379-86.
Anes E and Jordao L. 2008. Trick-or-treat: dietary lipids and host resistance to infectious disease. Mini Rev in Med Chem; 8(14): 1452-1458
Kuehnel M, Mayorga LS, Dandekar T, Thakar J, Schwarz R, Anes E, Griffiths G and Reich J. 2008. Modelling phagosomal lipid networks that regulate actin assembly. BMC Syst Biol,5; 2(1):107.
Gutierrez, MG*, Mishra, BB*, Jordao, ML, Elliot, E, Anes, E and Griffiths, G. 2008. NF-kappa B activation controls phago-lysosome fusion-mediated killing of mycobacteria by macrophages. J. Immunology 18(4): 2651-63 *joined first authors
Jordao, L., Bleck, CKE., Mayorga, L., Griffiths, G, and Anes, E. 2008. On the killing of mycobacteria by macrophages. Cell Microbiol 10(2): 529-48.
Anes, E., Peyron, P., Staali, L., Jordao, L., Gutierrez, M.G., Kress, H., Hagedorn, M., Maridonneau-Parini, I., Skinner, M.A., Wildeman, A.G., Kalamidas, S.A., Kuehnel, M. & Griffiths, G. 2006. Dynamic life and death interactions between Mycobacterium smegmatis and J774 macrophages. Cell Microbiol 8(6): 939-60.
Anes, E., Kuhnel, M.P., Bos, E., Moniz-Pereira, J., Habermann, A. & Griffiths, G. 2003. Selected lipids activate phagosome actin assembly and maturation resulting in killing of pathogenic mycobacteria. Nat Cell Biol; 5(9): 793-802.
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