In the shot gun used by T. cruzi to regulate the ECM interactome to gain cellular entry and evade the host reported here, T. cruzi gp83 triggers gp83 receptors in the cell via ERK1/2 to up-regulate LAMC1 which cross-talks with both LGALS3 and THBS1 to enhance cellular infection using selected parasite surface molecules such as TcCRT and TC45 mucin. Here, MAPK3 is linked to infection.