Noteworthy, when the complete invasion-differentiation-release cycle was evaluated in HL-1 cells overexpressing Rap1b-G12V (Fig 3E), trypomastigotes released into the medium showed similar results than the results obtained for percentage of infected cells and amastigotes/100cells (Fig 3C and 3D), suggesting the cAMP/Epac/Rap1b pathway would play a role in the early steps of the establishment of the infection, as previously hypothesized [7]. The gene discussed is RAP1B; the disease is infection.