While dendritic cells are major antigen-presenting cells and macrophage are the host, cytokine-producing cell and effector cell in infection by H. capsulatum, our study reveals that CR3 and Dectin-1 are of vital importance not only in their collaborative roles in macrophage cytokine production but also in instructing adaptive immune response against disseminated histoplasmosis. This evidence concerns the gene CRIPTO3 and infection.