TY - JOUR T1 - T Cell-Dependence of Lassa Fever Pathogenesis A1 - Flatz, Lukas A1 - Rieger, Toni A1 - Merkler, Doron A1 - Bergthaler, Andreas A1 - Regen, Tommy A1 - Schedensack, Mariann A1 - Bestmann, Lukas A1 - Verschoor, Admar A1 - Kreutzfeldt, Mario A1 - Brück, Wolfgang A1 - Hanisch, Uwe-Karsten A1 - Günther, Stephan A1 - Pinschewer, Daniel D. Y1 - 2010/03/26 N2 - Author Summary Lassa virus (LASV) is the causative agent of Lassa fever (LF), accounting for substantial morbidity and mortality in West Africa. Yet the mechanisms leading to disease remain poorly understood. Here we propose a concept whereby the body's immune defense either defeats LASV rapidly or, if unsuccessful, becomes an essential facilitator of disease. This latter paradoxical postulate stems from observations in genetically engineered (HHD) mice, which we found to be susceptible to LF. HHD mice differ from resistant wild type mice in that they have a humanized repertoire of T cells, a main component of the mammalian immune system. Counterintuitively, we could protect HHD mice against LF by experimentally removing their T cells. We further found that LF correlated with widespread activation of macrophages, which again depended on T cells. Similar to T cells, macrophages are important players in our body's defense system, but their inflammatory products are also candidate mediators of LF. Taken together, these findings suggest that LF may represent an inappropriate host response to infection. Specifically, our study demonstrates a two-faced role of T cell responses against LASV. Such detrimental aspects of immune defense need to be given consideration in future LF vaccine development, to avoid enhancement of disease in vaccinated individuals. JF - PLOS Pathogens JA - PLOS Pathogens VL - 6 IS - 3 UR - https://doi.org/10.1371/journal.ppat.1000836 SP - e1000836 EP - PB - Public Library of Science M3 - doi:10.1371/journal.ppat.1000836 ER -