Brucella abortus RNA does not polarize macrophages to a particular profile but interferes with M1 polarization

SERAFINO, AGUSTINA; MARIN FRANCO, JOSÉ L.; MAIO, MARIANO; TROTTA, ALDANA; GENOULA, MELANIE; CASTILLO, LUIS A.; BIRNBERG WEISS, FEDERICO; PITTALUGA, JOSÉ R.; BALBOA, LUCIANA; BARRIONUEVO, PAULA; MILILLO, M. AYELÉN

PLOS NEGLECTED TROPICAL DISEASES

PUBLIC LIBRARY SCIENCE

Año: 2022 vol. 16

1935-2735

Monocytes and macrophages play a central role in chronic brucellosis. Brucella abortus(Ba) is an intracellular pathogen that survives inside these cells. On the other hand, macrophages could be differentiated into classical (M1), alternative (M2) or other less-identifiedprofiles. We have previously shown that Ba RNA (a bacterial viability-associated PAMP orvita-PAMP) is a key molecule by which Ba can evade the host immune response. However,we did not know if macrophages could be polarized by this vita-PAMP. To assess this, weused two different approaches: we evaluated if Ba RNA per se was able to differentiate macrophages to M1 or M2 or, given that Ba survives inside macrophages once a Th1 responseis established (i.e., in the presence of IFN-γ), we also analysed if Ba RNA could interferewith M1 polarization. We found that Ba RNA alone does not polarize to M1 or M2 but activates human macrophages instead. However, our results show that Ba RNA does interferewith M1 polarization while they are being differentiated. This vita-PAMP diminished the M1-induced CD64, and MHC-II surface expression on macrophages at 48 h. This phenomenonwas not associated with an alternative activation of these cells (M2), as shown byunchanged CD206, DC-SIGN and CD163 surface expression. When evaluating glucosemetabolism, we found that Ba RNA did not modify M1 glucose consumption or lactate production. However, production of Nitrogen Reactive Species (NRS) did diminish in Ba RNAtreated M1 macrophages. Overall, our results show that Ba RNA could alter the properimmune response set to counterattack the bacteria that could persist in the host establishinga chronic infection.