Implication of purinergic P2X7 receptor in M. tuberculosis infection and host interaction mechanisms: A mouse model study

作者：Santos Andre A Jr; Rodrigues Junior Valnes; Zanin Rafael F; Borges Thiago J; Bonorino Cristina; Coutinho Silva Robson; Takyia Christina M; Santos Diogenes S; Campos Maria M; Morrone Fernanda B^*

来源：Immunobiology, 2013, 218(8): 1104-1112.

DOI：10.1016/j.imbio.2013.03.003

• ATP
• Mouse
• Mycobacterium tuberculosis
• P2X7 receptor
• RAW 264.7

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 F2X7R(-/-) 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. tuberculosis-infected 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.

• 出版日期2013-8