Granzymes in the fight against sepsis

Upon infection, our body initiates a process of inflammation that aims to effectively eliminate the threatening pathogen. However, when the process goes wrong, pathological situations may emerge such as in the case of sepsis. Sepsis refers to whole-body inflammation with life-threatening complications.

Emerging evidence indicates that granzymes, a family of proteases, contribute to sepsis. The scope of the EU-funded study 'The role of granzymes A, B and M in sepsis' (GRANZYMES IN SEPSIS) was to investigate the role of different granzymes in bacterial sepsis and identify which cells secrete them through both experimental and clinical approaches.

Using blood from healthy volunteers, patients with sepsis and systemic inflammatory response syndrome, scientists analysed the percentage of different lymphocyte populations expressing different granzymes (A, B, M and K). Similar work was performed in mouse models of sepsis and in patients with pulmonary tuberculosis.

Results showed that granzyme expression was linked to the process of inflammation and not the presence of bacteria per se. Natural killer cells were identified as the predominant population expressing these proteins. In tuberculosis patients, the granzyme levels were higher, similar to those observed during viral infections. Work in mice lacking one of the granzyme proteins suggested a role for these proteases in attenuating lung inflammation.

This protective role for granzymes in host defence against infection combined with information on their regulation opens up new avenues for their therapeutic exploitation. Future innovative treatments based on the manipulation of granzymes could serve as a means of inflammatory disease management.