Trypanosoma cruzi High Mobility Group B (TcHMGB) can act as an inflammatory mediator on mammalian cells

When an infection occurs, the innate immune cells recognize Pathogen Associated Molec ular Patterns (PAMPs) through their Pattern Recognition Receptors. This triggers an inflammatory response intended to kill the foreign microbe. But inflammation can also be triggered by the recognition of endogenous molecules called “Danger (or Damage) Asso ciated Molecular Patterns” (DAMPs) that are released by damaged or necrotic cells to “ring the alarm” of the immune system that repair is needed, so some of them are also known as “alarmins”. High Mobility group box 1 protein (HMGB1) is a prototypical alar min molecule released by injured cells and it is also actively secreted by cells of the innate immune system in response to invasion as well as to sterile damage. Trypanosoma cruzi, the causal agent of Chagas Disease, has its own HMGB protein that we called TcHMGB. Using in vitro and in vivo experimental systems, we demonstrated for the first time that TcHMGB is able to mediate inflammation on mammalian cells, inducing the expression of both pro-inflammatory and anti-inflammatory cytokines. Our results suggest that the parasite´s protein could have a role in the immune response and the pathogenesis of Cha gas disease, probably overlapping to some extent with the host cell DAMP molecules´ functions.