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Updated: Jun 9, 2025
An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Inhaled GM-CSF administered during ongoing pneumovirus infection alters myeloid and CD8 T cell immunity without
Nincy Debeuf1,2, Julie Deckers1,2, Sahine Lameire1,2
1Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
Abstract:
Granulocyte-macrophage colony stimulating factor (GM-CSF) is a pleiotropic cytokine, able to promote both myelopoiesis and activation of immune cells. Particularly in the lung, GM-CSF plays an important homeostatic role in the development and maintenance of alveolar macrophages, and is therefore considered to play a role in respiratory virus infections such as influenza and SARS-CoV-2, although the benefits of GM-CSF treatment in clinical studies remain inconclusive. To address this, we tested inhaled GM-CSF treatment in the Pneumonia Virus of Mice (PVM) mouse model. Our findings show that local GM-CSF therapy during PVM disease increased local neutrophilia and monocyte-derived cell influx, but diminished CD8+ T cells responses. Despite this, the observed effects on T cells and myeloid cells did not result in an altered clinical outcome during PVM infection. We conclude that inhaled GM-CSF therapy cannot be considered as a universal protective therapy in respiratory virus infections.
Insights
Inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy did not alter clinical outcomes in a mouse model of pneumonia virus of mice (PVM) infection, despite affecting immune cell responses.
Area of Science:
- Immunology
- Respiratory Medicine
- Infectious Diseases
Background:
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a key cytokine involved in immune cell development and activation.
- GM-CSF plays a critical role in lung homeostasis and is implicated in respiratory viral infections like influenza and SARS-CoV-2.
- The clinical efficacy of GM-CSF in respiratory viral infections remains uncertain.
Purpose of the Study:
- To investigate the therapeutic potential of inhaled GM-CSF in a mouse model of Pneumonia Virus of Mice (PVM) infection.
- To evaluate the impact of local GM-CSF therapy on immune cell populations and clinical outcomes during PVM infection.
Main Methods:
- Mice were treated with inhaled GM-CSF during PVM infection.
- Immune cell responses, including neutrophils, monocytes, and CD8+ T cells, were analyzed.
- Clinical outcomes of the infection were assessed.
Main Results:
- Inhaled GM-CSF therapy led to increased neutrophilia and monocyte-derived cell infiltration in the lungs.
- A decrease in CD8+ T cell responses was observed following GM-CSF treatment.
- Despite these immune modulations, GM-CSF treatment did not significantly alter the clinical outcome of PVM infection.
Conclusions:
- Local inhaled GM-CSF therapy does not provide a universal protective effect in respiratory viral infections.
- The complex effects of GM-CSF on myeloid and T cell responses may not translate to improved clinical outcomes in this model.
- Further research is needed to understand the specific contexts where GM-CSF may be beneficial in respiratory viral infections.
