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

PERDOMO V; HERNANDEZ-PANDO, ROGELIO; MANARIN R; CRIBB P; ALONSO V

Caxambu

Congreso; XXXIII Annual Meeting of the Brazilian Society of Protozoology / XLIV Annual Meeting on Basic Research in Chagas Disease; 2017

Brazilian Society of Protozoology

High Mobility Group B (HMGB) proteins are conserved nuclear architectural factors involved inchromatin remodeling and important nuclear events. HMGBs also play key roles outside the cellacting as alarmins or Damage Associated Molecular Patterns (DAMPs). In response to a damage ordanger signal these proteins act as immune mediators in the extracellular milieu. Moreover, DAMPsplay a central role in the pathogenesis of many autoimmune, infectious and inflammatory chronicdiseases.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 otherorganisms. The aim of this study was to determine if the parasite protein can also act as aninflammatory mediator as a first attempt to study its putative role in the pathogenesis of Chagasdisease. Using a recombinant TcHMGB protein, we observed that the parasite HMGB is able toinduce an inflammatory response in vitro and in vivo, evidenced by the production of Nitric Oxide andinduction 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, wereinduced by rTcHMGB. In order to play an inflammatory role during T. cruzi infection, TcHMGB isexpected to be secreted or released by the parasite. Indeed, we showed that TcHMGB can betranslocated to the cytoplasm and secreted out of the parasite, a process that seems to be stimulatedby acetylation. Additionally, immunohistochemistry in mice hearts during acute experimental T. cruziinfection showed high production of TcHMGB by amastigotes that appears to be secreted and coexistswith inflammatory cells and pro-inflammatory cytokines.These results suggest that TcHMGB can act as an exogenous immune mediator and can beenvisioned as a pathogen associated molecular pattern (PAMP) partially overlapping in function withthe host DAMPs Supported by:CONICET, ANPCYT, CONACYT Keywords:High mobility group b;danger associated molecular pattern; inflammation