7.3 - GILZ and bacterial infections
Recent findings from our group have shed light on the role of GILZ
during bacterial infections. Studies using GILZ knockout (KO) mice have
shown that these mice exhibit decreased bacterial clearance and enhanced
lung lesions when infected with Streptococcus pneumoniae .
Conversely, the introduction of a cell-permeable transactivator of
transcription (TAT)-GILZ fusion protein increased macrophage
phagocytosis and reduced bacterial load in the lungs (Souza et al.,
2022). TAT-GILZ treatment also enhanced macrophage influx with a
regulatory phenotype in a model of E. coli -induced peritonitis in
mice, accompanied by increased production of IL-10 and TGF-β levels,
efferocytosis and bacterial clearance (Grossi et al, 2023).
Intriguingly, monocytes isolated from septic patients displayed lower
expression of GILZ. However, when GILZ was overexpressed specifically in
macrophages and monocytes, bacterial clearance was enhanced in a cecal
ligation and puncture (CLP) mouse model (Ellouze et al., 2020).
Supporting these findings, upregulation of GILZ in immune cells was
associated with reduced mortality induced by lipopolysaccharide (LPS) in
mice (Ng et al., 2020). Conversely, downregulation of GILZ in
macrophages led to increased phagocytic activity during S.
typhimurium infection in vitro (Hoppstädter et al., 2019).
Therefore, the role of GILZ during bacterial infections appears to be
dependent on the specific cell type and bacterial strain. These results
suggest the potential for developing targeted treatments tailored to
specific bacterial strains in human infections. Drug delivery systems
that selectively upregulate GILZ levels in macrophages may be beneficial
in certain bacterial infections, rather than increasing its systemic
levels across all cell types. Nonetheless, further studies are needed to
gain a better understanding of these complex dynamics.