title: Implication of purinergic P2X7 receptor in M. tuberculosis infection and host interaction mechanisms: a mouse model study.
abstract: In the present study, we analyzed the role of purinergic P2X7 receptor in Mycobacterium tuberculosis infection and host interaction mechanisms in vitro and in vivo. For experimental procedures, a macrophage murine cell line RAW 264.7, and male Swiss, wild-type C57BL/6 and P2X7 receptor knockout (P2X7R−/−) mice were used throughout this study. We have demonstrated that treatment of RAW 264.7 cells with ATP (3 and 5 mM) resulted in a statistically significant reduction of M. tuberculosis-colony-forming units. The purinergic P2X7 receptor expression was found significantly augmented in the lungs of mice infected with M. tuberculosis H37Rv. Infected wild-type mice showed a marked increase in the spleen weight, in comparison to non-infected animals. Furthermore, M. tuberculosis-infected P2X7R−/− mice showed an increase of M. tuberculosis burden in lung tissue, when compared to infected wild-type mice. In P2X7R−/− spleens, we observed a significant decrease in the populations of Treg (CD4+Foxp3+), T cells (CD4+, CD8+CD25+ and CD4+CD25+), dendritic cells (CD11c+) and B220+ cells. However, a significant increase in CD11b+ cells was observed in P2X7R−/− mice, when compared to wild-type animals. In the lungs, P2X7R−/− M. tuberculosisinfected mice exhibited pulmonary infiltrates containing an increase of Treg cells (CD4+Foxp3+), T cells (CD4+ and CD8+) and a decrease in the B220+ cells, when compared with wild-type M. tuberculosis-infected mice. The findings observed in the present study provide novel evidence on the role of P2X7 receptors in the pathogenesis of tuberculosis.
authors.affiliation: Instituto Nacional de Ciência e Tecnologia em Tuberculose-INCT-TB, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: André A
authors.initials: AA
authors.lastname: Santos
authors.forename: Valnês
authors.initials: V
authors.lastname: Rodrigues-Junior
authors.forename: Rafael F
authors.initials: RF
authors.lastname: Zanin
authors.forename: Thiago J
authors.initials: TJ
authors.lastname: Borges
authors.forename: Cristina
authors.initials: C
authors.lastname: Bonorino
authors.forename: Robson
authors.initials: R
authors.lastname: Coutinho-Silva
authors.forename: Christina M
authors.initials: CM
authors.lastname: Takyia
authors.forename: Diógenes S
authors.initials: DS
authors.lastname: Santos
authors.forename: Maria M
authors.initials: MM
authors.lastname: Campos
authors.forename: Fernanda B
authors.initials: FB
authors.lastname: Morrone
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D008168:Lung / Q000378:metabolism / Q000382:microbiology; D018655:Lymphocyte Count; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology
chemical_list: D058486:Receptors, Purinergic P2X7