Leishmania major (L. major) is the most well-studied Leishmania species. Many classical studies on L. major have lead to the paradigm of Th1/Th2 dichotomy which has been a dogma in infectious disease research (137). Leishmania amazonensis (L. amazonensis), a New World species of Leishmania, cause a chronic diseases in many inbred mice with features distinct from L. major infection (105). A comparison in T cell response in these two infections has revealed defects in T cell response (105). However, a detailed study of dendrictic cell (DC) response during L. amazonensis infection has not been reported. Since DCs are the most potent antigen-presenting-cells (APC), a through understanding of DC defects will greatly facilitate our understanding of factors contributing to chronicity of L. amazonensis infection.;This dissertation focuses on the impairment of DC functions during L. amazonensis infection. Chapter 1 is a general introduction which includes the organization of dissertation and a regulates ERK activation which inhibit DC functions such as CD40 and IL-12 expression. NO is found to inhibit Th1 response in both L. amazonensis and L. major infections.