INVESTIGADORES
GIAMBARTOLOMEI Guillermo Hernan
congresos y reuniones científicas
Título:
B. abortus RNA induces MHC-I retention in the Golgi apparatus via TLR8 and by disrupting the acidification of this compartment.
Autor/es:
MARÍA AYELÉN MILILLO, ALDANA TROTTA, FÀBIO VITARELLI MARINHO, MARÍA VICTORIA DELPINO, LIS NOELIA VELÁSQUEZ, MONICA VERMEULEN, SERGIO COSTA OLIVEIRA, GUILLERMO GIAMBARTOLOMEI, PAULA BARRIONUEVO
Reunión:
Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017
Resumen:
Despite eliciting a potent CD8+ T cell response, Brucella abortus is able to persist andestablish a chronic infection inside its host. We have previously reported that the infectionof human monocytes/macrophages with B. abortus inhibits the IFN-γ-induced MHC-I cellsurface expression down-modulating cytotoxic CD8+ T cell responses. MHC-I down-modulationdepends on bacterial viability and results from the capacity of B. abortus to retainthe MHC-I molecules within the Golgi apparatus. Furthermore, we recently demonstratedthat epidermal growth factor receptor (EGFR) pathway is involved in this phenomenon andthat this is an early event during infection. However, the components and mechanismswhereby B. abortus is able to down-modulate MHC-I remained to be elucidated. In thisstudy we demonstrated that the down-modulation of MHC-I expression is not mediated bywell-known Brucella virulence factors but instead by B. abortus RNA, a PAMP associatedto viability (vita-PAMP). Surprisingly, completely degraded RNA was also able to inhibitMHC-I expression to the same extent as intact RNA. Accordingly, B. abortus RNA and itsdegradation products were able to mimic the MHC-I intracellular retention within the Golgiapparatus observed upon infection. We further demonstrated that TLR8, a single-strandedRNA and RNA degradation products sensor, was involved in MHC-I inhibition. On theother hand, neutralization of the EGFR reversed the MHC-I inhibition, suggesting a connectionbetween the TLR8 and EGFR pathways. Finally, B. abortus RNA-treated macrophagesdisplay diminished capacity of antigen presentation to CD8+ T cells. Overall, ourresults indicate that the vita-PAMP RNA as well as its degradation products constitutenovel virulence factors whereby B. abortus, by a TLR8-dependent mechanism andthrough the EGFR pathway, inhibits the IFN-γ-induced MHC-I surface expression on human monocytes/macrophages. Thus, bacteria can hide within infected cells and avoidthe immunological surveillance of cytotoxic CD8+ T cells.
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