Platelets Promote Brucella abortus Monocyte Invasion by Establishing Complexes With Monocytes

Abstract

Brucellosis is an infectious disease elicited by bacteria of the genus Brucella. Platelets have been extensively described as mediators of hemostasis and responsible for maintaining vascular integrity. Nevertheless, they have been recently involved in the modulation of innate and adaptive immune responses. Although many interactions have been described between Brucella abortus and monocytes/macrophages, the role of platelets during monocyte/macrophage infection by these bacteria remained unknown. The aim of this study was to investigate the role of platelets in the immune response against B. abortus. We first focused on the possible interactions between B. abortus and platelets. Bacteria were able to directly interact with platelets. Moreover, this interaction triggered platelet activation, measured as fibrinogen binding and P-selectin expression. We further investigated whether platelets were involved in Brucella-mediated monocyte/macrophage early infection. The presence of platelets promoted the invasion of monocytes/macrophages by B. abortus. Moreover, platelets established complexes with infected monocytes/macrophages as a result of a carrier function elicited by platelets. We also evaluated the ability of platelets to modulate functional aspects of monocytes in the context of the infection. The presence of platelets during monocyte infection enhanced IL-1β, TNF-α, IL-8, and MCP-1 secretion while it inhibited the secretion of IL-10. At the same time, platelets increased the expression of CD54 (ICAM-1) and CD40. Furthermore, we showed that soluble factors released by B. abortus-activated platelets, such as soluble CD40L, platelet factor 4, platelet-activating factor, and thromboxane A2, were involved in CD54 induction. Overall, our results indicate that platelets can directly sense and react to B. abortus presence and modulate B. abortus-mediated infection of monocytes/macrophages increasing their pro-inflammatory capacity, which could promote the resolution of the infection.

Brucella abortus-Stimulated Platelets Activate Brain Microvascular Endothelial Cells Increasing Cell Transmigration through the Erk1/2 Pathway

“…Platelets were obtained from whole blood from healthy adult human donors as described previously [ 14 ]. Briefly, blood samples were collected into tubes containing sodium citrate (Merck) and centrifuged.…”

“…Platelets are well characterized as responsible for maintaining vascular integrity in addition to being hemostatic mediators [ 12 ]. In the last few years, the immune function of platelets has been described in both homeostasis and pathology [ 12 , 13 , 14 ]. Platelets express several immune receptors such as toll-like receptors (TLR) and Fc receptors, which allow the recognition of different pathogens [ 12 ].…”

“…Upon pathogen recognition, platelets can be activated and secrete a wide variety of immunomodulatory mediators present in their granules [ 15 , 16 , 17 ]. The immunoregulatory functions of pathogen-activated platelets have been described recently, as well as their ability to activate endothelial cells, including the microvascular endothelium of the BBB [ 14 , 18 , 19 , 20 ]. We have recently described the interactions between platelets and B. abortus [ 14 ].…”

“…The immunoregulatory functions of pathogen-activated platelets have been described recently, as well as their ability to activate endothelial cells, including the microvascular endothelium of the BBB [ 14 , 18 , 19 , 20 ]. We have recently described the interactions between platelets and B. abortus [ 14 ]. B. abortus is able to invade, infect platelets, and activate them.…”

“…B. abortus is able to invade, infect platelets, and activate them. As a consequence of this interaction, platelets establish complexes with B. abortus -infected monocytes, increasing the efficiency of the infection and modulating monocyte and neutrophil functions [ 14 , 21 ]. Moreover, we demonstrated that complexes between platelets and both monocytes and neutrophils are more abundant in patients with brucellosis than in healthy donors [ 21 ].…”