FIGURES
Figure 1. Schematic view of the interplay between different cell
death modalities in the context of infection. During immune challenge,
in infected macrophages (A) an autophagic process can be triggered by
pathogen contact and the phagocyted microorganisms are targeted by an
ubiquitin coat to autophagosomes and then to autolysosomes to be
eliminated by acidic and enzymatic degradation. If microbes are
persistent or escape from vacuolar compartments, under apoptosis
blockade (for example by Caspase 8 inactivation) alternative cell death
programs can be activated, releasing the pathogen to be neutralized by
other immune cells, enhancing inflammation and activating the immune
system. Thus, the cell can go undergo autophagic cell death, necroptosis
induced by TLRs under Caspase 8 inhibition, through the RIPK1-RIPK3-MLKL
pathway or by Microbial DNA through DAI-RIPK3 interactions, or Caspase
1-dependent pyroptosis triggered by NOD receptors. On the other hand, in
infected neutrophils (B) pathogen contact triggers an apoptotic process
that ensures the safe disposal of the microbial components and toxins
after its degradation and at the same time regulates neutrophil
population during immune response. Alternatively, persistent pathogens
can also activate NETosis, through the ERK-NOX4 pathway, Massive
permeabilization and releasing of granules content cause neutrophil
death, but the released extracellular traps enclose and destroy invader
pathogens. TLRs: Toll-like receptors; RIPK: Receptor interacting protein
kinases; MLKL: Mixed lineage kinase domain-like protein; DAI:
DNA-dependent activator of IFN regulatory factors; PAMPs: Pathogen
associated molecular patterns; DAMPs: Danger associated molecular
patterns; NOD: Nucleotide-binding and oligomerization domain; GSDMD:
Gasdermine D; IL: Interleukine; ERK: Extracellular signal-regulated
kinase; NOX4: NAPH oxidase 4; ROS: Reactive oxigen species; MPO:
Myeloperoxidase; NE: Neutrophil elastase; PAD4: peptidylarginine
deiminase 4; NET: Neutrophil extracellular trap.