Brucella abortus RNA is the vita-PAMP employed by this bacterium to inhibit the IFN-γ-induced Major Histocompatibility Complex (MHC) molecules surface expression, evading the host immune response.

TROTTA A; BARRIONUEVO P; MILILLO MA; GIAMBARTOLOMEI GH; BALBOA L

Cancún

Congreso; XII Congress of the Latin American Association of Immunology - ALAI/ XXIII Congress of the Mexican Society of Immunology - SMI; 2018

ALAI y SMI

Brucella abortus is an intracellular pathogen capable of surviving inside macrophages.In order to persist inside the host and establish a chronic infection, this bacterium must trigger different strategies to evade the robust adaptive T cell response it elicits. Previously, we demonstrated that B. abortus inhibits the IFN-γ-induced surface expression of MHC-II on human monocytes.As a consequence, the infected macrophages show a reduction in antigen presentation to TCD4+ lymphocytes.B. abortus outer membrane lipoproteins ?a bacterial structural component- are involved in MHC-II down-modulation through the secretion of IL-6. Moreover, they are responsible for inhibiting the IFN-γ-induced transcription of the Class II Transactivator and MHC-II genes. Accordingly, we demonstrated that B. abortus-infected monocytes show a drastic reduction of MHC-II expression either in the surface or within the cell. Nevertheless, MHC-II down-modulation by B. abortus lipoproteins was less marked than the one observed with the infection. This last evidence led us think that there should have been another component associated to live bacteria implicated in MHC-II down-modulation. In fact, we have lately showed that B. abortus RNA, a PAMP associated to bacterial viability or vita-PAMP, is the component involved in MHC-I down-modulation. Inhibition of MHC-I expression was not due to changes in protein synthesis. Rather, this phenomenon results from the capacity of B. abortus RNA to retain the MHC-I molecules within the Golgi apparatus. In addition, we also discovered that the pathway associated with this event is the EGFR?s as EGF-like ligands could also reproduce MHC-I down-modulation observed in monocytes infected with B. abortus or stimulated with its RNA. Thus, the aim of this study was to analyse whether B. abortus RNA could also contribute toMHC-II down-modulation mediated by B. abortus. For this, human monocytic THP-1 cells were incubated with B. abortus RNA (1-10 µg/ml) in the presence of IFN-γ for 48 h. The expression of MHC-II molecules (HLA-DR) was then evaluated by flow cytometry. B. abortus RNA as well as RNase I-treated RNA significantly (p