Brucella abortus RNA polarizes macrophages towards a M1 profile at early time points but interferes with M1 polarization at later periods.

SERAFINO A; TROTTA A; MARÍN FRANCO JL; BALBOA L; BARRIONUEVO P; MILILLO MA

San Miguel de Tucumán

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Inmunología (SAI).; 2019

Monocytes and macrophages play a central role in chronic brucellosis. Brucella abortus (Ba) is an intracellular pathogen which survives inside these cells. Macrophages could differentiate from classical to alternative activation. We have showed that Ba RNA and TLR8 ligands promote the secretion of pro-inflammatory cytokines at short periods in macrophages. However, we ignore if these macrophages are polarized during Ba infection. In this work, we demonstrate that at 24 h, Ba RNA-treated macrophages showed up-regulation of M1 markers and secretion of pro-inflammatory cytokines. However, these M1 marker are down-regulated at longer periods post-stimulation. Ba RNA boosted (IFN-gamma +LPS)-induced CD86 expression and IL-1β secretion at 24 h, while it has no effect on (IFN-gamma +LPS)-induced MHC-II expression. It induces secretion of IL-10. Nevertheless, at 48 h Ba RNA diminished the (IFN-gamma + LPS)-induced MHC-II and CD86 surface expression as well as secretion of IL-1β. This phenomenon was associated with reduced functional capacities in M1 macrophages, such as antigen presentation and production of NOS. Ba RNA does not change M1 phenotype once it is already induced. Overall, these results indicate that B. abortus through its RNA alters the functionality of M1 macrophages, which could lead to the persistence of infection in the host.