DEVELOPMENTAL ADAPTATIONS OF TRYPANOSOMA CRUZI TO THE VERTEBRATE IMMUNE SYSTEM

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In this project we have been studying developmental adaptations of T. cruzi to the vertebrate host and, in particular the molecular basis of adaptive changes occurring during the differentiation of epimastigotes (vector stage) to metacyclic trypomastigotes (infective stage). A. Studies on developmental control of intracellular survival in macrophages Epimastigotes were shown to enter mouse macrophages by CR3 receptors while the entry and survival of metacyclic trypomastigotes was shown to be enhanced by complement but also to depend on fibronectin receptors. B. Analysis of stage-specific gene expression in metacyclic forms Metacyclic stage specific cDNA's were cloned from T. cruzi and L. major. Sequence analysis indicated that the principal T. cruzi clone has homology with a c-fos proto-oncogene while the L. major clone has homology with beta-chain of RNA polymerase.