HIGH MOBILITY GROUP B FROM TRYPANOSOMA CRUZI: A PUTATIVE INFLAMMATORY MEDIATOR IN ACUTE CHAGAS

CRIBB P; PERDOMO V; MANARIN R; ALONSO VL; HERNANDEZ-PANDO R

Caxambu

Congreso; XXIII Annual Meeting of the Brazilian Society of Protozoology; 2017

Sociedade Brasileira de Protozoologia

High Mobility Group B (HMGB) proteins are conserved nuclear architectural factors involved in chromatin remodeling and important nuclear events. HMGBs also play key roles outside the cell acting as alarmins or Damage Associated Molecular Patterns (DAMPs). In response to a damage or danger signal these proteins act as immune mediators in the extracellular milieu. Moreover, DAMPs play a central role in the pathogenesis of many autoimmune, infectious and inflammatory chronic diseases. We have previously identified a High mobility group B protein from Trypanosoma cruzi (TcHMGB) and showed that it has architectural properties interacting with DNA like HMGBs from other organisms. The aim of this study was to determine if the parasite protein can also act as an inflammatory mediator as a first attempt to study its putative role in the pathogenesis of Chagas disease. Using a recombinant TcHMGB protein, we observed that the parasite HMGB is able to induce an inflammatory response in vitro and in vivo, evidenced by the production of Nitric Oxide and induction of inflammatory cytokines like TNF-α, IL-1β and IFN-γ gene expression. Interestingly, TGF-β and IL-10, which are not inflammatory cytokines but do play key roles in Chagas disease, were induced by rTcHMGB. In order to play an inflammatory role during T. cruzi infection, TcHMGB is expected to be secreted or released by the parasite. Indeed, we showed that TcHMGB can be translocated to the cytoplasm and secreted out of the parasite, a process that seems to be stimulated by acetylation. Additionally, immunohistochemistry in mice hearts during acute experimental T. cruzi infection showed high production of TcHMGB by amastigotes that appears to be secreted and co-exists with inflammatory cells and pro-inflammatory cytokines. These results suggest that TcHMGB can act as an exogenous immune mediator and can be envisioned as a pathogen associated molecular pattern (PAMP) partially overlapping in function with the host DAMPs