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Updated: Jun 19, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Evasion by stealth: inefficient immune activation underlies poor T cell response and severe disease in
Jincun Zhao1, Jingxian Zhao, Nico Van Rooijen
1Department of Microbiology, University of Iowa, Iowa City, Iowa, USA.
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.
Insights
Alveolar macrophages impair immune responses during severe respiratory infections. Depleting these cells or activating them corrects immune defects, improving survival in a mouse model of SARS.
Area of Science:
- Immunology
- Virology
- Respiratory Medicine
Background:
- Severe Acute Respiratory Syndrome (SARS) caused significant illness and death globally.
- A mouse-adapted SARS virus (MA15) replicates human disease features, including high morbidity and mortality in BALB/c mice.
Purpose of the Study:
- To investigate the role of respiratory dendritic cells (rDCs) and alveolar macrophages (AMs) in SARS pathogenesis.
- To identify therapeutic strategies to improve immune responses and survival in a mouse model of SARS.
Main Methods:
- MA15 infection in BALB/c mice.
- Assessment of virus clearance, rDC activation and migration, and T cell responses.
- Treatment with clodronate liposomes to deplete AMs.
- Activation of AMs and rDCs using poly I:C.
- Adoptive transfer of bone marrow-derived dendritic cells (BMDCs).
Main Results:
- Severe SARS disease correlated with slow virus clearance and delayed rDC activation/migration, leading to poor T cell responses.
- Depletion of AMs using clodronate liposomes corrected these immune defects and improved survival.
- Poly I:C pretreatment activated AMs and rDCs, nullifying inhibitory AM effects.
- Adoptive transfer of activated BMDCs protected mice from lethal MA15 infection.
Conclusions:
- Alveolar macrophages play an inhibitory role in the immune response to SARS-CoV infection.
- Targeting AMs or enhancing DC function may be a viable therapeutic strategy for severe respiratory viral infections like SARS.
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