T cell-dependence of Lassa fever pathogenesis.

Lassa virus (LASV), the causative agent of Lassa fever (LF), is endemic in West Africa, accounting for substantial morbidity and mortality. In spite of ongoing research efforts, LF pathogenesis and mechanisms of LASV immune control remain poorly understood. While normal laboratory mice are resistant...

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Autores principales:	Lukas Flatz, Toni Rieger, Doron Merkler, Andreas Bergthaler, Tommy Regen, Mariann Schedensack, Lukas Bestmann, Admar Verschoor, Mario Kreutzfeldt, Wolfgang Brück, Uwe-Karsten Hanisch, Stephan Günther, Daniel D Pinschewer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1fd1372c1c1d49f0804b35f627226502
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spelling	oai:doaj.org-article:1fd1372c1c1d49f0804b35f6272265022021-11-25T05:48:13ZT cell-dependence of Lassa fever pathogenesis.1553-73661553-737410.1371/journal.ppat.1000836https://doaj.org/article/1fd1372c1c1d49f0804b35f6272265022010-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20360949/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Lassa virus (LASV), the causative agent of Lassa fever (LF), is endemic in West Africa, accounting for substantial morbidity and mortality. In spite of ongoing research efforts, LF pathogenesis and mechanisms of LASV immune control remain poorly understood. While normal laboratory mice are resistant to LASV, we report that mice expressing humanized instead of murine MHC class I (MHC-I) failed to control LASV infection and develop severe LF. Infection of MHC-I knockout mice confirmed a key role for MHC-I-restricted T cell responses in controlling LASV. Intriguingly we found that T cell depletion in LASV-infected HHD mice prevented disease, irrespective of high-level viremia. Widespread activation of monocyte/macrophage lineage cells, manifest through inducible NO synthase expression, and elevated IL-12p40 serum levels indicated a systemic inflammatory condition. The absence of extensive monocyte/macrophage activation in T cell-depleted mice suggested that T cell responses contribute to deleterious innate inflammatory reactions and LF pathogenesis. Our observations in mice indicate a dual role for T cells, not only protecting from LASV, but also enhancing LF pathogenesis. The possibility of T cell-driven enhancement and immunopathogenesis should be given consideration in future LF vaccine development.Lukas FlatzToni RiegerDoron MerklerAndreas BergthalerTommy RegenMariann SchedensackLukas BestmannAdmar VerschoorMario KreutzfeldtWolfgang BrückUwe-Karsten HanischStephan GüntherDaniel D PinschewerPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 3, p e1000836 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Lukas Flatz Toni Rieger Doron Merkler Andreas Bergthaler Tommy Regen Mariann Schedensack Lukas Bestmann Admar Verschoor Mario Kreutzfeldt Wolfgang Brück Uwe-Karsten Hanisch Stephan Günther Daniel D Pinschewer T cell-dependence of Lassa fever pathogenesis.
description	Lassa virus (LASV), the causative agent of Lassa fever (LF), is endemic in West Africa, accounting for substantial morbidity and mortality. In spite of ongoing research efforts, LF pathogenesis and mechanisms of LASV immune control remain poorly understood. While normal laboratory mice are resistant to LASV, we report that mice expressing humanized instead of murine MHC class I (MHC-I) failed to control LASV infection and develop severe LF. Infection of MHC-I knockout mice confirmed a key role for MHC-I-restricted T cell responses in controlling LASV. Intriguingly we found that T cell depletion in LASV-infected HHD mice prevented disease, irrespective of high-level viremia. Widespread activation of monocyte/macrophage lineage cells, manifest through inducible NO synthase expression, and elevated IL-12p40 serum levels indicated a systemic inflammatory condition. The absence of extensive monocyte/macrophage activation in T cell-depleted mice suggested that T cell responses contribute to deleterious innate inflammatory reactions and LF pathogenesis. Our observations in mice indicate a dual role for T cells, not only protecting from LASV, but also enhancing LF pathogenesis. The possibility of T cell-driven enhancement and immunopathogenesis should be given consideration in future LF vaccine development.
format	article
author	Lukas Flatz Toni Rieger Doron Merkler Andreas Bergthaler Tommy Regen Mariann Schedensack Lukas Bestmann Admar Verschoor Mario Kreutzfeldt Wolfgang Brück Uwe-Karsten Hanisch Stephan Günther Daniel D Pinschewer
author_facet	Lukas Flatz Toni Rieger Doron Merkler Andreas Bergthaler Tommy Regen Mariann Schedensack Lukas Bestmann Admar Verschoor Mario Kreutzfeldt Wolfgang Brück Uwe-Karsten Hanisch Stephan Günther Daniel D Pinschewer
author_sort	Lukas Flatz
title	T cell-dependence of Lassa fever pathogenesis.
title_short	T cell-dependence of Lassa fever pathogenesis.
title_full	T cell-dependence of Lassa fever pathogenesis.
title_fullStr	T cell-dependence of Lassa fever pathogenesis.
title_full_unstemmed	T cell-dependence of Lassa fever pathogenesis.
title_sort	t cell-dependence of lassa fever pathogenesis.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/1fd1372c1c1d49f0804b35f627226502
work_keys_str_mv	AT lukasflatz tcelldependenceoflassafeverpathogenesis AT tonirieger tcelldependenceoflassafeverpathogenesis AT doronmerkler tcelldependenceoflassafeverpathogenesis AT andreasbergthaler tcelldependenceoflassafeverpathogenesis AT tommyregen tcelldependenceoflassafeverpathogenesis AT mariannschedensack tcelldependenceoflassafeverpathogenesis AT lukasbestmann tcelldependenceoflassafeverpathogenesis AT admarverschoor tcelldependenceoflassafeverpathogenesis AT mariokreutzfeldt tcelldependenceoflassafeverpathogenesis AT wolfgangbruck tcelldependenceoflassafeverpathogenesis AT uwekarstenhanisch tcelldependenceoflassafeverpathogenesis AT stephangunther tcelldependenceoflassafeverpathogenesis AT danieldpinschewer tcelldependenceoflassafeverpathogenesis
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T cell-dependence of Lassa fever pathogenesis.

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