Bacterial RNA Contributes to the Down-Modulation of MHC-II Expression on Monocytes/Macrophages Diminishing CD4+ T Cell Responses

MILILLO, M. AYELÉN; TROTTA, ALDANA; SERAFINO, AGUSTINA; MARIN FRANCO, JOSÉ LUIS; MARINHO, FÁBIO V.; ALCAIN, JULIETA; GENOULA, MELANIE; BALBOA, LUCIANA; COSTA OLIVEIRA, SERGIO; GIAMBARTOLOMEI, GUILLERMO H., THIS AUTHOR CONTRIBUTED EQUALLY; BARRIONUEVO, PAULA

Frontiers in Immunology

Frontiers Media SA

Lugar: Lausana; Año: 2019 vol. 10

Brucella abortus, the causative agent of brucellosis, displays many resources to evade Tcell responses conducive to persist inside the host. Our laboratory has previously showedthat infection of human monocytes with B. abortus down-modulates the IFN-g-inducedMHC-II expression. Brucella outer membrane lipoproteins are structural componentsinvolved in this phenomenon. Moreover, IL-6 is the soluble factor that mediated MHC-IIdown-regulation. Yet, the MHC-II down-regulation exerted by lipoproteins was lessmarked than the one observed as consequence of infection. This led us to postulate thatthere should be other components associated with viable bacteria that may act togetherwith lipoproteins in order to diminish MHC-II. Our group has recently demonstrated thatB. abortus RNA (PAMP related to pathogens? viability or vita-PAMP) is involved in MHC-Idown-regulation. Therefore, in this study we investigated if B. abortus RNA could becontributing to the down-regulation of MHC-II. This PAMP significantly down-modulatedthe IFN-g-induced MHC-II surface expression on THP-1 cells as well as in primaryhuman monocytes and murine bone marrow macrophages. The expression of othermolecules up-regulated by IFN-g (such as co-stimulatory molecules) was stimulatedon monocytes treated with B. abortus RNA. This result shows that this PAMP doesnot alter all IFN-g-induced molecules globally. We also showed that other bacterial andparasitic RNAs caused MHC-II surface expression down-modulation indicating that thisphenomenon is not restricted to B. abortus. Moreover, completely degraded RNA wasalso able to reproduce the phenomenon. MHC-II down-regulation on monocytes treatedwith RNA and L-Omp19 (a prototypical lipoprotein of B. abortus) was more pronouncedthan in monocytes stimulated with both components separately. We also demonstratedthat B. abortus RNA along with its lipoproteins decrease MHC-II surface expressionpredominantly by a mechanism of inhibition of MHC-II expression. Regarding thesignaling pathway, we demonstrated that IL-6 is a soluble factor implicated in B. abortusRNA and lipoproteins-triggered MHC-II surface down-regulation. Finally, CD4+ T cells functionality was affected as macrophages treated with these components showedlower antigen presentation capacity. Therefore, B. abortus RNA and lipoproteins aretwo PAMPs that contribute to MHC-II down-regulation on monocytes/macrophagesdiminishing CD4+ T cell responses.