Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 39, Pages 15496-15501Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0707454104
Keywords
hantavirus; TGF; zoonosis; immunopathology; Peromyscus
Categories
Funding
- NIAID NIH HHS [1U01 AI054779, U19 AI045452, U01 AI056618, 2 U19 AI45420, AI054461, R15 AI054461, U01 AI054779, R56 AI034448, N01AI25489, U01 AI56618] Funding Source: Medline
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Hantavirus cardiopulmonary syndrome is a zoonotic illness associated with a systemic inflammatory immune response, capillary leak, noncardiogenic pulmonary edema, and shock in humans. Cytokines, including TNF, IFN-gamma, and lymphotoxin, are thought to contribute to its pathogenesis. In contrast, infected rodent reservoirs of hantaviruses experience few or no pathologic changes and the host rodent can remain persistently infected for life. Generally, it is unknown why such dichotomous immune responses occur between humans and reservoir hosts. Thus, we examined CD4(+) T cell responses from one such reservoir, the deer mouse (Peromyscus maniculatus), infected with Sin Nombre virus. Proliferation responses to viral nucleocapsid antigen were relatively weak in T cells isolated from deer mice, regardless of acute or persistent infection. The T cells from acutely infected deer mice synthesized a broad spectrum of cytokines, including IFN-gamma, IL-4, IL-5, and TGF-beta(1), but not TNF, lymphotoxin, or IL-17. However, in T cells from persistently infected deer mice, only TGF-beta(1) was expressed by all lines, whereas some expressed reduced levels of IFN-gamma or IL-5. The Forkhead box P3 transcription factor, a marker of some regulatory T cells, was expressed by most of these cells. Collectively, these data suggest that TGF-beta(1)-expressing regulatory T cells may play an important role in limiting immunopathology in the natural reservoir host, but this response may interfere with viral clearance. Such a response may have arisen as a mutually beneficial coadaptive evolutionary event between hantaviruses and their rodent reservoirs, so as to limit disease while also allowing the virus to persist.
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