B. ABORTUS RNA ACTIVATES MACROPHAGES TOWARDS A PRO-INFLAMMATORY PROFILE EARLY ON DURING INFECTION

SERAFINO, AGUSTINA; MARIN, JOSE LUIS; CASTILLO, LUIS ALEJANDRO; BIRNBERG-WEISS, FEDERICO; PITTALUGA, JOSE R.; BALBOA, LUCIANA; BARRIONUEVO, PAULA; MILILLO, AYELEN

Virtual

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIAS 2021; 2021

B. ABORTUS RNA ACTIVATES MACROPHAGES TOWARDS A PRO-INFLAMMATORYPROFILE EARLY ON DURING INFECTIONAgustina Serafino, José L. Marin Franco, Luis A. Castillo, Federico Birnberg-Weiss, José R. Pittaluga,Luciana Balboa, Paula Barrionuevo, M. Ayelén Milillo.Laboratorio de Fisiología de los Procesos Inflamatorios, IMEX-CONICET, Academia Nacional deMedicina.KEY WORDS: B. abortus, RNA, M1, M2, immune evasionBrucellosis is a zoonotic disease caused by Brucella spp bacteria. These pathogens cansurvive inside macrophages, persisting inside the host. We previously demonstrated thatBrucella abortus (Ba) RNA is a PAMP involved in the immune evasion mediated by Ba. Oneof the mechanisms displayed by this bacterium is the down-modulation of MHC moleculeswhen Th1 response is being held, i.e., in the presence of IFN-Ɣ. Nevertheless, weacknowledged whether Ba RNA could activate macrophages early on during the infection,before Th1 response is settled. To evaluate this, M0 (undifferentiated) macrophages werestimulated with Ba RNA (10 μg/ml) and at 24 and 48 h M1 (classical macrophages) or M2(alternative macrophages) markers were assessed by flow cytometry. Regarding M1markers, CD86 and MHC-II expressions did not change neither at 24 nor 48 h. Surprisingly,CD64 expression was reduced in Ba RNA treated macrophages (p<0.05). Ba RNAstimulates the secretion of pro-inflammatory cytokines (IL-8, TNF-ɑ and IL-1β) only at 24 h(p<0.05). With respect to M2 markers, CD206 expression was reduced at 48 h in Ba RNA-treated macrophages (p<0.05) but DC-SIGN and CD163 expressions did not changecompared to untreated cells. Ba RNA induced IL-10 secretion, mostly at 24 h (p<0.05). Wealso performed functionality assays of M1 macrophages. Nitrite Oxide production (assessedby Griess reaction) was stimulated in Ba RNA treated macrophages at 24 h (p<0.05).Moreover, glucose consumption and lactate production were also augmented by Ba RNA(p<0.05), all hallmarks of M1 profile. These results show that Ba RNA can activatemacrophages into a pro-inflammatory profile -at least for a short time- early on duringinfection. These results also lay the ground for studying more deeply the modulatoryproperties of bacterial RNA in the context of brucellosis, other intracellular infections andtumors.