Severe Human Lassa Fever Is Characterized by Nonspecific T-Cell Activation and Lymphocyte Homing to Inflamed Tissues
Julia R. Port, David M. Wozniak, Lisa Oestereich, Elisa Pallasch, Beate Becker‐Ziaja, Jonas Müller, Monika Rottstegge, Catherine Olal, Sergio Gómez‐Medina, Jennifer Oyakhliome, Yemisi Ighodalo, Emmanuel Omomoh, Thomas Olokor, Donatus I. Adomeh, Danny Asogun, Ephraim Ogbani-Emovon, Kristin Hartmann, Susanne Krasemann, Emily V. Nelson, Beatriz Escudero-Pérez, Anita K. McElroy, Stephan Günther, César Muñoz‐Fontela
Abstract
Lassa fever may cause severe disease in humans, in particular in areas of endemicity like Sierra Leone and Nigeria. Despite its public health importance, the pathophysiology of Lassa fever in humans is poorly understood. Here, we present clinical immunology data obtained in the field during the 2018 Lassa fever outbreak in Nigeria indicating that severe Lassa fever is associated with activation of T cells antigenically unrelated to Lassa virus and poor Lassa virus-specific effector T-cell responses. Mechanistically, we show that these bystander T cells express defined tissue homing signatures that suggest their recruitment to inflamed tissues and a putative role of these T cells in immunopathology. These findings open a window of opportunity to consider T-cell targeting as a potential postexposure therapeutic strategy against severe Lassa fever, a hypothesis that could be tested in relevant animal models, such as nonhuman primates.