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Updated: Jan 18, 2026
Isolation and In Vitro Culture of Murine and Human Alveolar Macrophages
Published on: April 20, 2018
Helping alveolar macrophages live to fight another day during viral pneumonia
Elise Mr Armstrong1,2, Joseph P Mizgerd1,2,3,4
1Pulmonary Center.
Abstract:
Alveolar macrophages (AMs) help defend the lungs against infection, but during pneumonia many alveolar macrophages die. In this issue of the JCI, Malainou et al. explored the mechanism underpinning AM death during viral pneumonia and its effect on the outcomes of bacterial superinfection, a secondary infection that occurs before the first infection is cleared. In mouse models of influenza A infection, recruited neutrophils secreted TNF superfamily member 14 (TNFSF14), and AMs increased expression of the TNFSF14 receptors TNFSFR14 and type I transmembrane lymphotoxin β receptor (LTβR). TNFSF14 signaling via the LTβR was sufficient to cause AM apoptosis. TNFSF14 deficiency or blockade preserved AMs during influenza infection and diminished bacterial burdens and mouse mortality during pneumococcal superinfection. The adoptive transfer of AMs decreased the severity of pneumococcal superinfections, if those AMs lacked the LTβR. Thus, preserving AMs by interrupting TNFRSF14-LTβR interactions can make virus-infected lungs less susceptible to severe bacterial superinfection.
Insights
During viral pneumonia, neutrophils trigger alveolar macrophage (AM) death via TNFSF14 signaling. Blocking this pathway preserves AMs, reducing severe bacterial superinfections and mortality in mice.
Area of Science:
- Immunology
- Pulmonology
- Microbiology
Background:
- Alveolar macrophages (AMs) are crucial for lung defense against infection.
- Pneumonia often leads to significant AM death, impairing lung immunity.
- Bacterial superinfections following viral pneumonia can have severe outcomes.
Purpose of the Study:
- To investigate the mechanism of AM death during viral pneumonia.
- To determine the role of AM death in bacterial superinfection severity.
- To explore therapeutic strategies for preventing superinfections.
Main Methods:
- Mouse models of influenza A infection.
- Analysis of immune cell signaling pathways, including TNFSF14 and its receptors.
- Assessment of bacterial burden and mortality following superinfection.
- Adoptive transfer of AMs with modified receptor expression.
Main Results:
- Neutrophils in influenza-infected lungs secrete TNFSF14, inducing AM apoptosis via LTβR signaling.
- TNFSF14 deficiency or blockade protected AMs during influenza infection.
- Interruption of TNFSF14-LTβR interaction reduced bacterial superinfection severity and mortality.
- AMs lacking LTβR conferred protection when adoptively transferred.
Conclusions:
- TNFSF14-LTβR signaling is a key driver of AM apoptosis during viral pneumonia.
- Preserving AMs by blocking this pathway mitigates severe bacterial superinfections.
- Targeting the TNFSF14-LTβR axis offers a potential therapeutic strategy for viral-bacterial coinfections.
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