Chapters authored
Novel Insights into the Pathophysiology of Chagas' Cardiomyopathy
The protozoan hemoflagellate Trypanosoma cruzi (T. cruzi) is the etiologic agent of the zoonotic Chagas’ disease that affects approximately six to seven million people in Central and South America, causing dilated cardiomyopathy and megavisceral disease. Although Chagas’ disease is the leading cause of heart failure in Latin America among people living in poverty and places an immense socioeconomic burden on society, it is still currently classified as a neglected tropical disease (NTD). The disease is typically transmitted by reduviid bugs or orally by contaminated food, while the transmission of parasitic organisms by other routes such as blood transfusion, organ transplantation, and transplacental infection is relatively rare. Given the wide cellular tropism infecting virtually all nucleated cells, the protozoan is able to persist asymptomatically for decades until ultimately causing organ-specific symptoms of chronic Chagas’ disease such as chronic heart failure. The acute phase of the disease triggers an immune response that often does not restrict the dissemination of the parasite and may cause skin lesions, fever, enlarged lymph nodes, pallor, swelling, and abdominal and chest pain. Despite recent advances in our knowledge about the pathogenesis of this disease, the complex host-parasite interactions are not completely understood and, in particular, the persistence of parasites in host cells for such a long time remains largely undefined. In this book chapter, we focus on the pathophysiology of American trypanosomiasis and emphasize the role of host-specific transcription factors executing antiparasitic immune reactions.
Part of the book: Cardiomyopathies
Gene Activation by the Cytokine-Driven Transcription Factor STAT1
Signal transducers and activators of transcription (STATs) are a family of cytokine-regulated transcription factors, which serve the dual role of external signal transduction and transcriptional activation. The founding member of this family, STAT1, is involved in a plethora of cellular processes, including interferon-dependent upregulation of various effector mechanisms in immune and non-immune cells to control bacterial, fungal and parasitic infections. In this chapter, we discuss the principles of STAT1-driven gene expression and focus on the clinical phenotypes of various human STAT1 mutations. In particular, we highlight the significance of sequence-specific DNA binding and intact nucleocytoplasmic shuttling for full transcriptional activation of interferon-driven target genes.
Part of the book: Gene Regulation