3.4 Complement system
When the host recognizes the danger signal, the complement system will be activated. Complement can regulate the early innate immune response, which is essential to protect the host from the uncontrolled transmission of invasive pathogens. In the early stage of sepsis, complement-related activated products will increase, such as anaphylactoid toxins C3a, C4A, and c5a[35]. Complement activation products C3a, C5a, and c5b induce anti-microbial response and pro-inflammatory effect through crosstalk with a variety of signal transduction pathways. With the progress of complement activation, continuous production of C5a may lead to congenital immune paralysis, resulting in weakened inflammation and bacterial killing[36]. C5a and C5aR can induce an inflammatory response and participate in multiple organ failures during sepsis. Sommerfeld[37] et al. Found that in the mild to moderate sepsis model, c5ar1 deficient mice had a higher survival rate than the wild group, and the c5ar1 deficient group could also improve liver injury in sepsis. In addition, complement-mediated neutrophil dysfunction, apoptosis, and systemic inflammatory response also affect the progression of sepsis.