Granzyme K synergistically potentiates LPS-induced cytokine responses in human monocytes

Granzymes are serine proteases released by cytotoxic lymphocytes and induce cell death in virus-infected cells and tumor cells. However, granzymes also exist extracellularly in the blood circulation of patients with autoimmune diseases and infections and may contribute to inflammation. Here, we show that human granzyme K (GrK) binds to Gram-negative bacteria and to lipopolysaccharide (LPS), a Gram-negative bacterial cell wall component. Our data indicate that GrK lowers the threshold for monocyte activation by LPS, in that GrK synergistically increases LPS-induced release of proinflammatory cytokines in vitro and in vivo. In conclusion, GrK modulates the innate immune response against LPS and Gram-negative bacteria and may contribute to the pathogenesis of diseases associated with a local or systemic bacterial infection.