Home Economics American Trypanosomiasis Chagas Disease, Second Edition: One Hundred Years of Research
Invasion of nonphagocytic host cells and the concomitant activation of the innate immune response are among the earliest interactions between T. cruzi and its mammalian host. An integrated model of nonphagocytic cell invasion by T. cruzi is currently favored, which reconciles previously described invasion routes originally considered to be mechanistically independent. Importantly, although it is well established that parasite-triggered signaling cascades initiated by interaction with host cell surface molecules are required for invasion, attaining integrated understanding of the relationship between these signaling events and the different components of the emerging invasion model constitutes a remaining challenge to be tackled in future research efforts.
T. cruzi invasion of nonphagocytic host cells results in the activation of the innate immune system, specifically type I IFN production, which in turn drives the global transcriptional profile of infected cells and influences the subsequent adapta- tive immune response. The signaling mechanisms leading to type I IFN production during T. cruzi infection remain poorly understood. Furthermore, the degree to which these early events determine the outcome of the infection with T. cruzi is currently unknown, although under conditions of high parasite burden, type I IFN production is detrimental for the host.83 A negative effect of type I IFN responses is in line with a trend found for infection with other intracellular pathogens, such as mycobacteria and Leishmania, and gaining a better understanding of these phenomena may provide clues to new therapeutic options and strategies for prognosis of the clinical manifestations of Chagas disease. Finally, further studies are warranted in order to gain broader understanding of the impact that the full breath of genetic variability of T. cruzi might have over individual aspects of infection such as cell invasion and type I IFN responses, and how this might in turn impact the overall immune responses and the clinical outcomes of chagasic patients.
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