Helping alveolar macrophages live to fight another day during viral pneumonia
Elise M.R. Armstrong, Joseph P. Mizgerd
Elise M.R. Armstrong, Joseph P. Mizgerd
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Commentary

Helping alveolar macrophages live to fight another day during viral pneumonia

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.

Authors

Elise M.R. Armstrong, Joseph P. Mizgerd

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Figure 1

During influenza pneumonia, neutrophil-derived TNFSF14 uses the LTβR to trigger AM apoptosis, which increases susceptibility to severe bacterial superinfection.

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During influenza pneumonia, neutrophil-derived TNFSF14 uses the LTβR to ...
Studies by Malainou et. al. showed that neutrophils in the influenza-infected lung produced TNFSF14, whereas AMs increased expression of the TNFSF14 receptors TNFRSF14 and LTβR. TNFSF14 stimulated AM apoptosis primarily through the LTβR (8). These AM-depleted, influenza-infected lungs were susceptible to severe pneumococcal superinfection. However, deficiency of TNFSF14 during influenza infection (or its blockade prior to pneumococcal infection) made bacterial superinfection less severe. Although the adoptive transfer of WT or TNFRSF14-deficient AMs did not alter superinfection severity, the adoptive transfer of AMs lacking the LTβR (hence resistant to TNSF14-induced apoptosis) was sufficient to minimize the severity of superinfection. BMDM, bone marrow–derived macrophage.