1. Severe human Lassa fever is characterized by non-specific T-cell activation and lymphocyte homing to inflamed tissues.
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Port, Julia R., Wozniak, David M., Oestereich, Lisa, Pallasch, Elisa, Becker-Ziaja, Beate, Müller, Jonas, Rottstegge, Monika, Olal, Catherine, Gómez-Medina, Sergio, Oyakhliome, Jennifer, Ighodalo, Yemisi, Omomoh, Emmanuel, Olokor, Thomas, Adomeh, Donatus I., Asogun, Danny, Ogbani-Emovon, Ephraim, Hartmann, Kristin, Krasemann, Susanne, Nelson, Emily V., and Escudero-Pérez, Beatriz
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LASSA fever , *LYMPHOCYTE transformation , *HEMORRHAGIC fever , *PATHOLOGY , *CLINICAL immunology , *T cells - Abstract
Lassa fever (LF) is a zoonotic viral hemorrhagic fever caused by Lassa virus (LASV), which is endemic to West African countries. Previous studies have suggested an important role for T cell-mediated immunopathology in LF pathogenesis, but the mechanisms by which T cells influence disease severity and outcome are not well understood. Here we present a multiparametric analysis of clinical immunology data collected during the 2017-2018 Lassa fever outbreak in Nigeria. During the acute phase of LF we observed robust activation of the polyclonal T-cell repertoire, which included LASV-specific as well as antigenically-unrelated T cells. However, severe and fatal LF were characterized by poor LASV-specific effector T-cell responses. Severe LF was also characterized by the presence of circulating T cells with homing capacity to inflamed tissues, including the gut mucosa. These findings in LF patients were recapitulated in a mouse model of LASV infection, in which mucosal exposure resulted in remarkably high lethality compared to skin exposure. Taken together, our findings indicate that poor LASV-specific T-cell responses and activation of non-specific T cells with homing capacity to inflamed tissues are associated with severe LF. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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