Evasion by stealth: inefficient immune activation underlies poor T cell response and severe disease in SARS-CoV-infected mice

Jincun Zhao; Jingxian Zhao; Nico Van Rooijen; Stanley Perlman

doi:10.1371/journal.ppat.1000636

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Evasion by stealth: inefficient immune activation underlies poor T cell response and severe disease in SARS-CoV-infected mice

Journal article

Open access

Peer reviewed

Evasion by stealth: inefficient immune activation underlies poor T cell response and severe disease in SARS-CoV-infected mice

Jincun Zhao, Jingxian Zhao, Nico Van Rooijen and Stanley Perlman

PLoS pathogens, Vol.5(10), pp.e1000636-e1000636

10/2009

DOI: 10.1371/journal.ppat.1000636

PMCID: PMC2762542

PMID: 19851468

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Abstract

Severe Acute Respiratory Syndrome caused substantial morbidity and mortality during the 2002-2003 epidemic. Many of the features of the human disease are duplicated in BALB/c mice infected with a mouse-adapted version of the virus (MA15), which develop respiratory disease with high morbidity and mortality. Here, we show that severe disease is correlated with slow kinetics of virus clearance and delayed activation and transit of respiratory dendritic cells (rDC) to the draining lymph nodes (DLN) with a consequent deficient virus-specific T cell response. All of these defects are corrected when mice are treated with liposomes containing clodronate, which deplete alveolar macrophages (AM). Inhibitory AMs are believed to prevent the development of immune responses to environmental antigens and allergic responses by interacting with lung dendritic cells and T cells. The inhibitory effects of AM can also be nullified if mice or AMs are pretreated with poly I:C, which directly activate AMs and rDCs through toll-like receptors 3 (TLR3). Further, adoptive transfer of activated but not resting bone marrow-derived dendritic cells (BMDC) protect mice from lethal MA15 infection. These results may be relevant for SARS in humans, which is also characterized by prolonged virus persistence and delayed development of a SARS-CoV-specific immune response in individuals with severe disease.

SARS Virus - immunology

Myeloablative Agonists - pharmacology

T-Lymphocytes - physiology

Macrophages, Alveolar - pathology

Dendritic Cells - immunology

Severe Acute Respiratory Syndrome - immunology

Dendritic Cells - physiology

Virus Latency - drug effects

Virus Latency - physiology

Lymphocyte Activation - immunology

Liposomes - therapeutic use

Mice, Inbred C57BL

Severe Acute Respiratory Syndrome - mortality

Severe Acute Respiratory Syndrome - drug therapy

Immune Evasion - physiology

Disease Progression

Severe Acute Respiratory Syndrome - prevention & control

Animals

Macrophages, Alveolar - drug effects

T-Lymphocytes - immunology

Clodronic Acid - administration & dosage

Mice

Mice, Inbred BALB C

Virus Latency - immunology

Immune Evasion - immunology

Details

Title: Subtitle: Evasion by stealth: inefficient immune activation underlies poor T cell response and severe disease in SARS-CoV-infected mice
Creators: Jincun Zhao - Department of Microbiology, University of Iowa, Iowa City, Iowa, USA
Jingxian Zhao
Nico Van Rooijen
Stanley Perlman
Resource Type: Journal article
Publication Details: PLoS pathogens, Vol.5(10), pp.e1000636-e1000636
DOI: 10.1371/journal.ppat.1000636
PMID: 19851468
PMCID: PMC2762542
NLM abbreviation: PLoS Pathog
ISSN: 1553-7366
eISSN: 1553-7374
Publisher: United States
Grant note: P01 AI060699 / NIAID NIH HHS
Language: English
Date published: 10/2009
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777347402771

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