PLATELETS DIRECTLY INTERACT WITH Brucella abortus AND MODULATE INFECTED HUMAN MONOCYTES TOWARDS A PRO-INFLAMMATORY PROFILE

ALDANA TROTTA; M. AYELÉN MILILLO; M. VICTORIA DELPINO; LIS N. VELÁSQUEZ; ANA M. RODRÍGUEZ; GUILLERMO H. GIAMBARTOLOMEI; ROBERTO G. POZNER; PAULA BARRIONUEVO

Congreso; Reunión Conjunta de Biociencias 2017.; 2017

Brucellosis is an infectious disease elicited by bacteria of the genusBrucella. Platelets have been described as mediators of hemostasis.However, they have recently got involved in the modulationof innate and adaptive immune responses. We have previouslyreported that platelets modulate B. abortus-mediated infection ofhuman monocytes. The first aim of this study was to characterizethe interaction between platelets and B. abortus. For this, humanplatelets were co-incubated with B. abortus-GFP for 4 h and the interactionwas quantified by confocal microscopy and flow cytometry.Our results showed that platelets are able to interact with bacteriain a dose-dependent fashion. Moreover, this interaction stimulatedplatelet activation, measured as fibrinogen binding and P-selectinexpression (p<0.001). The next aim was to further analyze the abilityof platelets to modulate functional aspects of infected monocytes. Toaddress this, THP-1 cells were infected with B. abortus in presenceor absence of platelets for different times. The supernatants frominfected cells were collected and quantified by ELISA. The presenceof platelets during monocytes/macrophages infection stimulated IL-1β, TNF-α, IL-8 and MCP-1 secretion (p<0.001) while it inhibited thesecretion of IL-10 (p<0.01). We have previously demonstrated thatplatelets stimulated the expression of ICAM-1 (CD54) in monocytessurface. In order to investigate this mechanism, monocytes werestimulated with supernatants from B. abortus-infected platelets andsurface CD54 was measured by flow cytometry. Our results showthat CD54 induction is due to soluble factors released by infectedplatelets (p<0.001) and sCD40L and PAF are two of the mediatorsinvolved. Overall, our results indicate that platelets can directlysense and react to B. abortus presence. Moreover, they modulatethe B. abortus-infected monocytes increasing their pro-inflammatorycapacity, which could promote the resolution of the infection.