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Profa. Dra. Maria Regina D’Império Lima

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Título: Professor Livre Docente
Laboratório: Laboratório Imunologia das Infecções
Telefone: 55 (11) 3091-7389/3091-7374
E-mail: relima@usp.br
Lattes: http://lattes.cnpq.br/9054250993836740

Publons: https://publons.com/researcher/1758434/maria-regina-dimperio-lima

Equipe

Doutorado:

Mestrado:

Iniciação Científica: 

Técnico:

Linha de pesquisa

Estudo dos mecanismos moleculares envolvidos na ativação do sistema imune em modelos experimentais de infecções (malária, tuberculose e doença de Chagas).

Study of molecular mechanisms involved in activation of the immune system in experimental models of infections (malaria, tuberculosis and Chagas´disease).

Resumo

A malária, a tuberculose e a doença de Chagas são responsáveis por quase dois milhões de mortes anuais em todo o mundo. Estes agentes infecciosos vêm criando inúmeros desafios aos pesquisadores que estudam os aspectos imunológicos associados, tanto ao desenvolvimento da doença, como à geração de imunidade protetora. A nossa pesquisa tem como objetivo principal avaliar os mecanismos envolvidos na resposta imune precoce e tardia em modelos experimentais destas doenças infecciosas.

Malaria, tuberculosis and Chagas´ disease are responsible for nearly two million deaths annually worldwide. These infectious agents have created numerous challenges for researchers who study the immunological aspects associated with both the development of the disease and the generation of protective immunity. Our research aims to assess the mechanisms involved in early and late immune responses in experimental models of these infectious diseases.

Principais publicações

  1. Santiago-Carvalho, I.; Almeida-Santos, G.; Barbosa Bomfim, C. C.; Carolina de Souza, P.; Santos E Silva, J. C.; Silva de Melo, B. M.; Pinheiro Amaral, E.; Pinheiro Cione, M. V.; Lasunskaia, E.; Hirata, M. H. Farias Alves-Filho, J. C.; Nakaya, H. I.; Alvarez, J. M.; D’Império Lima, M. R. P2x7 receptor signaling blockade reduces lung inflammation and necrosis during severe experimental tuberculosis. Frontiers in Cellular and Infection Microbiology, 11:672472, 2021.
  2. Bomfim, C. C. B.; Amaral, E. P.; Carvalho, I. S.; Santos, G. A., Salles, E. M.; Hastreiter, A. A.; Nascimento, R. S.; Almeida, F. M.; Ventura Simão, T. L. B.; Rezende, A. L.; Hirata, M. H.; Fock, R. A.; Álvarez, J. M.; Lasunskaia, E.; D’Império Lima, M. R. Harmful effects of granulocytic myeloid-derived suppressor cells on tuberculosis caused by hypervirulent mycobacteria. Journal of Infectious Diseases, 223(3): 494-507, 2020.
  3. Menezes, M. N.; Salles, E. M.; Vieira, F., Amaral, E. P.; Zuzarte-Luís, V.; Cassado, A.; Epiphanio, S.; Álvarez, J. M.; Alves-Filho, J. C.; Mota, M. M.; D’Império-Lima, M. R. IL-1α promotes liver inflammation and necrosis during blood-stage Plasmodium chabaudi malaria. Scientific Reports, 9(1): 7575, 2019.
  4. Amaral, E. P.; Bomfim, C. C.; Salles, E. M.; Salgado, R. M.; Álvarez, J. M. M.; Hirata, M. H.; Lasunskaia, E. B., D’Império Lima, M. R. Inhibiting adenosine receptor signaling promotes accumulation of effector CD4+ T cells in the lung parenchyma during severe tuberculosis. Journal of Infectious Diseases, 219(6): 964-974, 2019.
  5. Borges da Silva, H.; Salles, E. M.; Faquim-Mauro, E.; Sardinha, L. R.; Álvarez, J. M.; D’Império Lima, M. R. CD28 deficiency leads to accumulation of germinal-center independent IgM+ experienced B cells and to production of protective IgM during experimental malaria. PLoS One, 13(8):e0202522, 2018.
  6. Salles, E. M.; Menezes, M. N.; Borges da Silva, H.; Amaral, E. P.; Castillo-Méndez, S. I.; Cassado, A. A.; Vieira, F. S.; Olivieri, D. N.; Tadokoro, C. E.; Álvarez, J. M.; Coutinho-Silva, R.; D’Império Lima, M. R. P2X7 receptor drives Th1 cell differentiation and controls the follicular helper T cell population to protect against experimental malaria. PLoS Pathogens, 13(8): e1006595, 2017.
  7. Bomfim, C. C. B.; Amaral, E. P.; Cassado, A. A.; Salles, E. M.; Nascimento, R. S.; Hirata, M. H.; Álvarez, J. M. M.; D’Império Lima, M. R. P2X7 receptor expression in bone-marrow-derived cells aggravates tuberculosis caused by hypervirulent Mycobacterium bovis. Frontiers in Immunology, 8: 435, 2017.
    Amaral, E. P.; Lasunskaia, E. B.; D’Império Lima, M. R. Innate immunity in tuberculosis: how the sensing of mycobacteria and tissue damage modulates macrophage death. Microbes and Infection, 18: 11-20, 2016.
  8. Borges da Silva, H.; Fonseca, R.; Álvarez, J. M.; D’Império Lima, M. R. IFN-γ priming effects on the maintenance of effector memory CD4(+) T cells and on phagocyte function: evidences from infectious diseases. Journal of Immunology Research 2015: 202816, 2015.
  9. Borges da Silva, H.; Fonseca, R.; Cassado, A. A.; Salles M. E.; de Menezes, M. N.; Langhorne, J.; Perez, K. R.; Cuccovia, I. M.; Ryffel, B.; Barreto, V. M.; Marinho, C. R.; Boscardin, S. B.; Álvarez, J. M., Tadokoro, C. E.; D’Império-Lima, M. R. In vivo approaches reveal a key role for DCs in CD4+ T cell activation and parasite clearance during the acute phase of experimental blood-stage malaria. PLoS Pathogens 11: e1004598, 2015.
  10. Borges da Silva, H.; Fonseca, R.; Pereira, R. M.; Cassado, A. A.; Álvarez, J. M.; D’Império Lima, M. R. Splenic macrophage subsets and their function during blood-borne infections. Frontiers in Immunology, 6: 480, 2015.
  11. Álvarez, J. M.; Fonseca, R.; Borges da Silva, H.; Marinho, C. R.; Bortoluci, K. R.; Sardinha, L. R.; Epiphanio, S.; D’Império Lima, M. R. Chagas disease: still many unsolved issues. Mediators of Inflammation, 2014: 912965, 2014.
  12. Amaral, E. P.; Andrade, M. R. M.; Ribeiro, S. C. M.; Lanes, V. R.; Almeida, F. M.; Salles, E. M.; Bortoluci, K. R.; Coutinho-Silva, R.; Hirata, M. H.; Álvarez, J. M. M.; Lasunskaia, E. B.; D’Império Lima, M. R. Pulmonary infection with hypervirulent mycobacteria reveals a crucial role for the P2X7 receptor in aggressive forms of tuberculosis. PLoS Pathogens 10: e1004188, 2014.
  13. Borges da Silva, H; de Salles, E. M.; Panatieri, R. H.; Boscardin, S. B.; Rodríguez-Málaga, S. M.; Álvarez, J. M.; D’Império Lima, M. R. IFN-γ-induced priming maintains long-term strain-transcending immunity against blood-stage Plasmodium chabaudi malaria. Journal of Immunology, 191: 5160-9, 2013.
  14. Zago, C. A.; Bortoluci, K. R.; Sardinha, L. R.; Pretel, F. D.; Castillo-Méndez, S. I.; Freitas do Rosário, A. P.; A, Hiyane, M. I.; Muxel, S. M.; Rodriguez-Málaga, S. M.; Abrahamsohn, I. A.; Álvarez, J. M.; D’Império Lima, M. R. Anti-IL-2 treatment impairs the expansion of Treg cell population during acute malaria and enhances the Th1 cell response at the chronic disease. PLoS One, 7: e29894, 2012.
  15. Sandra, S. M.; Freitas do Rosário, A. P.; Zago, C. A.; Castillo-Méndez S. I.; Sardinha, L. R.; Rodriguez-Málaga, S. M.; Niels Olsen, S. C.; Álvarez, J. M.; D’Império Lima, M. R. The Spleen CD4+ T cell response to blood-stage Plasmodium chabaudi malaria develops in two phases characterized by different properties. PLoS One, 6: e22434, 2011.
  16. Muxel, S. M.; Freitas do Rosário, A. P.; Sardinha, L. R.; Castillo-Méndez, S. I.; Zago, C. A.; Rodriguez-Málaga, S. M.; Álvarez, J. M., D’Império Lima, M. R. Comparative analysis of activation phenotype, proliferation and IFN- production by spleen NK1.1+ and NK1.1- T cells during Plasmodium chabaudi AS malaria. Journal of Interferon & Cytokine Research, 30: 55 – 64, 2010.
  17. Freitas do Rosario, A. P.; Muxel, S. M.; Rodriguez-Málaga, S. M.; Sardinha, L. R.; Zaga, C. A.; Castillo-Méndez, S. I,; Álvarez, J. M.; D’Império Lima, M. R. Gradual decline in malaria-specific memory T-cell responses leads to failure to maintain long-term protective immunity to Plasmodium chabaudi AS despite persistence of B-cell memory and circulating antibody. Journal of Immunology, 181: 8344 – 8355, 2008.
  18. Castillo-Méndez, S. I.; Zago, C. A.; Sardinha, L. R.; Freitas do Rosário, A. P.; Álvarez, J. M.; D’Império Lima, M. R. Characterization of the spleen B-cell compartment at the early and late blood-stage Plasmodium chabaudi malaria. Scandinavian Journal of Immunology, 66: 309-19, 2007.
  19. Bastos, K. R. B.; Barboza, R.; Sardinha, L.; Russo, M.; Álvarez, J. M.; D’ Império Lima, M. R. Role of endogenous IFN- in macrophage programming induced by IL-12 and IL-18. Journal of Interferon and Cytokine Research, 27: 399-410, 2007.
  20. Elias, R. M.; Sardinha, L. R.; Bastos, K. R. B.; Zago, C. A.; Freitas da Silva, A. P., Álvarez, J. M.; D’Império Lima, M. R. Role of CD28 in Polyclonal and specific T and B cell responses required for protection against blood stage malaria. Journal of Immunology, 174: 790-799, 2005.
  21. Bastos, K. R. B.; Vieira de Moraes, L.; Zago, C. A.; Marinho, C. R. F.; Russo, M.; Álvarez, J. M.; D’Império Lima, M. R. Analysis of the activation profile of dendritic cells derived from the bone marrow of IL-12/IL-23-deficient mice. Immunology, 114: 499-506, 2005.
  22. Bastos, K. R. B.; Marinho, C. R. F.; Barboza, R.; Russo, M.; Álvarez, J. M.; D’Império Lima, M. R. What kind of message does IL-12/IL-23 bring to macrophages and dendritic cells? Microbes and Infection, 6: 630-636, 2004.
  23. Bastos, K. R. B.; Álvarez, J. M.; Marinho, C. R. F.; Grisotto, M. G.; Rizzo, L. V.; D’Império Lima, M. R. Macrophages from IL-12-deficient mice have a bias towards the M2 activation profile. Journal of Leukocyte Biology, 71: 271-8, 2002.
  24. Bastos, K. R. B.; Barboza, R.; Elias, R. M.; Sardinha, L. R.; Grisotto, M. G.; Marinho, C. R. F.; Amarante-Mendes, G. P.; Álvarez, J. M.; D’Império Lima, M. R. Impaired macrophage responses may contribute to exacerbation of blood-stage Plasmodium chabaudi chabaudi malaria in IL-12-deficient mice. Journal of Interferon and Cytokine Research, 22: 1191-1199, 2002.
  25. Furtado, G. C.; Moura, I.; Pudles, J.; Álvarez, J. M.; D’Império Lima, M. R. A monoclonal antibody raised agaist Plasmodium chabaudi chabaudi soluble antigens present in the plasma of infected mice recognizes a 250 kDa schizont glycoprotein that is secreted during schizogony. Experimental Parasitology, 91: 97-100, 1999.
  26. Cavinato, R. A.; Bastos, K. R. B.; Sardinha, L. R.; Elias, R. M.; Álvarez, J. M.; D’Império Lima, M. R. Susceptibility of the different blood forms of Plasmodium chabaudi chabaudi to hyperimmune serum, IgG1, IgG2a and F(ab’)2 fragments. Parasite Immunology, 23: 587-97, 2001.
  27. D’Império Lima, M. R.; Álvarez, J. M.; Furtado, G. C.; Kipnis, T. L.; Coutinho, A; Minóprio, P. Ig-isotype patterns of polyclonal and parasite-specific B cell responses to Plasmodium chabaudi chabaudi correlate with IFN and IL-4 interleukin production and with CD45RB expression by CD4+ spleen cells. Scandinavian Journal of Immunology, 43: 263-270, 1996.
  28. D’Império Lima, M. R.; Bandeira, A.; Falanga, P.; Freitas, A. A.; Kipnis, T.L.; Pereira da Silva, L.; Coutinho, A. Clonal analysis of B lymphocyte responses to Plasmodium chabaudi infection of normal and immunoprotected mice. International Immunology, 3: 1207-1216, 1991.
  29. Falanga, P. B.; D’Império Lima, M. R.; Coutinho, A.; Pereira da Silva, L. Isotypic pattern of the polyclonal B cell response during primary infection by Plasmodium chabaudi in normal and immune-protected mice. European Journal of Immunology, 17: 599-603, 1987.
  30. D’Império Lima, M. R.; Eisen, H.; Minóprio, P.; Joskowicz, M.; Coutinho, A. Persistence of polyclonal B cell activation with undetectable parasitemia in late stages of experimental Chagas’ disease. Journal of Immunology, 137: 353-356, 1986.
  31. D’Império Lima, M. R.; Joskowicz, M.; Coutinho, A.; Kipnis, T.; Eisen, H. Very large and isotypically atypical polyclonal plaque forming cell response in mice infected with Trypanosoma cruzi. European Journal of Immunology, 15: 201-203, 1985.

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