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Susceptibility of Mycobacterium tuberculosis-infected CCR4 deficient mice is associated with a balance between lymphocytes and Foxp3+ regulatory cells

2013; Frontiers Media; Volume: 4; Linguagem: Inglês

10.3389/conf.fimmu.2013.02.00103

1664-3224

Bertolini Tha�s, Pi�eros Annie, Prado Rafael, Gembre Ana Fl�via, Alves-Filho Jos� Carlos, Bonato V�nia,

Cytokine Signaling Pathways and Interactions

Event Abstract Back to Event Susceptibility of Mycobacterium tuberculosis-infected CCR4 deficient mice is associated with a balance between lymphocytes and Foxp3+ regulatory cells Thaís B. Bertolini1*, Annie R. Piñeros1, Rafael Q. Prado1, Ana Flávia Gembre1, José Carlos Alves-Filho2 and Vânia L. Bonato1 1 Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil 2 Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil The control of M. tuberculosis infection requires granuloma formation as consequence of the leukocyte recruitment, partially dependent on chemokine and chemokine receptor. The pattern of chemokine and chemokine receptor expression drives the recruitment of specific leukocyte populations, including lymphocyte subsets. Chemokine receptor 4 (CCR4) is mostly expressed in Th2 CD4+ cells and CD4+Foxp3+ cells. The aim of this study was to assessment the participation of CCR4 in response to pulmonary infection with M. tuberculosis. CCR4 deficient (CCR4-/-) and wild type (WT) mice were infected with 1x105 bacilli by intra-tracheal route. Seventy days post-infection, Colony-Forming Unit (CFU) number in the lung and spleen, cell subsets and cytokine production were evaluated in the lungs of CCR4-/- and WT mice. At the chronic phase (70 days), CCR4-/- (n=14) mice were more susceptible to M. tuberculosis infection compared to WT (n=14) mice (p<0.05). In addition, 70-day infected CCR4-/- mice showed an increase in the total number of CD4+ and CD8+ cells, an increase in the frequency of CD8+ cells, followed by a decrease in the frequency of NK and CD4+Foxp3+ cells compared with WT mice. The lungs of infected CCR4-/- mice also exhibited a significant reduction of IL-17 and production of IFN-γ higher than those observed in infected WT mice. These data show that CCR4 plays a key role at the chronic phase of the infection and suggest that the balance between T lymphocytes and Foxp3+ regulatory cells may drive the resistance for tuberculosis. Acknowledgements School of Medicine of Ribeirão Preto, University of São Paulo, Bazil. Financial supporte: FAPESP, CAPES, FAEPA References Iellem, A., M. Mariani, R. Lang, H. Recalde, P. Panina-Bordignon, F. Sinigaglia and D. D'Ambrosio (2001). "Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells." J Exp Med 194(6): 847-853. Morais Fonseca, D., R. S. Rosada, M. O. e Paula, P. F. Wowk, L. H. Franco, E. G. Soares, C. L. Silva and V. L. Deperon Bonato (2010). "Experimental tuberculosis: designing a better model to test vaccines against tuberculosis." Tuberculosis (Edinb) 90(2): 135-142. Paula, M. O., D. M. Fonseca, P. F. Wowk, A. F. Gembre, P. F. Fedatto, C. A. Sérgio, C. L. Silva and V. L. Bonato (2011). "Host genetic background affects regulatory T-cell activity that influences the magnitude of cellular immune response against Mycobacterium tuberculosis." Immunol Cell Biol 89(4): 526-534. Scott-Browne, J. P., S. Shafiani, G. Tucker-Heard, K. Ishida-Tsubota, J. D. Fontenot, A. Y. Rudensky, M. J. Bevan and K. B. Urdahl (2007). "Expansion and function of Foxp3-expressing T regulatory cells during tuberculosis." J Exp Med 204(9): 2159-2169. Shafiani, S., G. Tucker-Heard, A. Kariyone, K. Takatsu and K. B. Urdahl (2010). "Pathogen-specific regulatory T cells delay the arrival of effector T cells in the lung during early tuberculosis." J Exp Med 207(7): 1409-1420. Stolberg, V. R., B. C. Chiu, B. M. Schmidt, S. L. Kunkel, M. Sandor and S. W. Chensue (2011). "CC chemokine receptor 4 contributes to innate NK and chronic stage T helper cell recall responses during Mycobacterium bovis infection." Am J Pathol 178(1): 233-244. Keywords: susceptibility, lymphocyte recruitment, Mycobacterium tuberculosis, Chemokine receptors, CCR4 Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune receptors and signaling Citation: Bertolini TB, Piñeros AR, Prado RQ, Gembre A, Alves-Filho J and Bonato VL (2013). Susceptibility of Mycobacterium tuberculosis-infected CCR4 deficient mice is associated with a balance between lymphocytes and Foxp3+ regulatory cells. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00103 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Miss. Thaís B Bertolini, Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil, thabarboza@yahoo.com.br Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Thaís B Bertolini Annie R Piñeros Rafael Q Prado Ana Flávia Gembre José Carlos Alves-Filho Vânia L Bonato Google Thaís B Bertolini Annie R Piñeros Rafael Q Prado Ana Flávia Gembre José Carlos Alves-Filho Vânia L Bonato Google Scholar Thaís B Bertolini Annie R Piñeros Rafael Q Prado Ana Flávia Gembre José Carlos Alves-Filho Vânia L Bonato PubMed Thaís B Bertolini Annie R Piñeros Rafael Q Prado Ana Flávia Gembre José Carlos Alves-Filho Vânia L Bonato Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.