T cell-dependence of Lassa fever pathogenesis.

Details

Serval ID
serval:BIB_138C99C027BA
Type
Article: article from journal or magazin.
Collection
Publications
Title
T cell-dependence of Lassa fever pathogenesis.
Journal
Plos Pathogens
Author(s)
Flatz L., Rieger T., Merkler D., Bergthaler A., Regen T., Schedensack M., Bestmann L., Verschoor A., Kreutzfeldt M., Brück W., Hanisch U.K., Günther S., Pinschewer D.D.
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Publication state
Published
Issued date
2010
Volume
6
Number
3
Pages
e1000836
Language
english
Abstract
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.
Keywords
Animals, Arenavirus/immunology, Interleukin-12 Subunit p40/immunology, Interleukin-12 Subunit p40/metabolism, Lassa Fever/immunology, Lassa Fever/prevention & control, Lassa virus/immunology, Macrophages/immunology, Macrophages/metabolism, Major Histocompatibility Complex/genetics, Major Histocompatibility Complex/immunology, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Monocytes/immunology, Monocytes/metabolism, T-Lymphocytes/immunology, T-Lymphocytes/virology, Viral Vaccines/immunology, beta 2-Microglobulin/genetics, beta 2-Microglobulin/immunology
Pubmed
Web of science
Open Access
Yes
Create date
23/03/2012 19:22
Last modification date
20/08/2019 13:42
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