CD47 expression attenuates Ebola virus-induced immunopathology in mice
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Updated: Oct 9, 2025
Isolation and Quantification of Zika Virus from Multiple Organs in a Mouse
Published on: August 15, 2019
Deepashri Rao1, Kyle L O'Donnell2, Aaron Carmody3
1Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Abstract:
It has been shown that a very early cell-intrinsic response to infection is the upregulation of CD47 cell surface expression, a molecule known for delivering a "don't eat me signal" that inhibits macrophage-mediated phagocytosis and antigen presentation. Thus, blockade of CD47 signaling during lymphocytic choriomenigitis virus infections of mice has been shown to enhance the kinetics and potency of immune responses, thereby producing faster recovery. It seems counterintuitive that one of the earliest responses to infection would be immunoinhibitory, but it has been hypothesized that CD47 induction acts as an innate immune system checkpoint to prevent immune overactivation and immunopathogenic responses during certain infections. In the current study we examined the effect of CD47 blockade on lethal Ebola virus infection of mice. At 6 days post-infection, CD47 blockade was associated with significantly increased activation of B cells along with increases in recently cytolytic CD8+ T cells. However, the anti-CD47-treated mice exhibited increased weight loss, higher virus titers, and succumbed more rapidly. The anti-CD47-treated mice also had increased inflammatory cytokines in the plasma indicative of a "cytokine storm". Thus, in the context of this rapid hemorrhagic disease, CD47 blockade indeed exacerbated immunopathology and disease severity.
Insights
Blocking CD47, a "don't eat me" signal, during Ebola virus infection in mice worsened disease. This blockade increased immune cell activation but led to more severe pathology and faster mortality, suggesting CD47 plays a protective role in this context.
Area of Science:
- Immunology
- Virology
- Pathology
Background:
- CD47 is a cell surface protein that signals "don't eat me", inhibiting phagocytosis and antigen presentation.
- Upregulation of CD47 is an early response to infection, potentially acting as an innate immune checkpoint to prevent overactivation.
- Previous studies showed CD47 blockade enhances immune responses in lymphocytic choriomenigitis virus infections.
Purpose of the Study:
- To investigate the effect of CD47 blockade on lethal Ebola virus infection in a mouse model.
- To determine if inhibiting CD47 signaling impacts disease severity and immune responses during Ebola virus infection.
Main Methods:
- Mice were infected with a lethal dose of Ebola virus.
- Anti-CD47 antibody treatment was administered post-infection.
- Immune cell activation (B cells, CD8+ T cells), viral load, weight loss, survival, and plasma cytokine levels were assessed.
Main Results:
- CD47 blockade increased B cell activation and cytolytic CD8+ T cell populations.
- However, anti-CD47 treated mice showed increased weight loss, higher virus titers, and succumbed more rapidly.
- Elevated inflammatory cytokines, indicative of a "cytokine storm", were observed in treated mice.
Conclusions:
- In the context of lethal Ebola virus infection, CD47 blockade exacerbated immunopathology and disease severity.
- The "don't eat me" signal of CD47 appears to be protective against severe disease and excessive inflammation in this model.
- CD47 blockade is not beneficial and may be detrimental in treating rapid hemorrhagic viral diseases like Ebola.
