LIPOPOLYSACCHARIDE MODULATES THE CHEMOKINE RECEPTORS CCR2 AND CX3CR1 AND INDUCES RECRUITMENT OF LEUKOCYTES TO THE CENTRAL NERVOUS SYSTEM

PERALTA-RAMOS JAVIER M; GAVIGLIO EMILIA A; ARROYO DANIELA S; BUSSI CLAUDIO; RODRIGUEZ GALÁN MARÍA C; IRIBARREN PABLO

Mar del Plata

Congreso; LXII Reunión Anual de la Sociedad Argentina de Inmunología; 2014

Sociedad Argentina de Inmunología

Microglial cells (MC) are components of the immune system intrinsic to the central nervous system (CNS) and they participate in responses induced by infection, aseptic inflammation, injury and/or neurodegeneration. These cells migrate to injury sites in response to chemoattractant agents that are produced under inflammatory circumstances. This response greatly depends on the expression and function of chemokine receptors. In this work, we evaluate the role of TLR4 in the regulation of the expression and function of chemoattractant receptors important in the recruitment of phagocytes and neuroinflammation such as CCR2 and CX3CR1. First of all, the study of the modulation of chemokine receptors in the CNS after a systemic pro-inflammatory stimulus with lipopolysaccharide (LPS), revealed a decreased gene expression of CX3CR1 and CX3CL1 in mice total brain under these conditions (p<0.05). On the other hand, we evaluated the induction of neuroinflammation, activation of MC and recruitment of leukocytes to the CNS. We observed an increase in the absolute number of MC, neutrophils, lymphocytes, dendritic cells and inflammatory monocytes in LPS-treated mice (p<0.001). Besides, we noted recruited monocytes showed CX3CR1 intracellularly and in the membrane, and intracellular CCR2, but only half of them expressed CCR2 in the membrane (p<0.001). Similarly, although the majority of MC displayed CX3CR1 intracellularly and in the membrane, and most of CCR2 was expressed intracellularly, only a low frequency of these cells exhibited this receptor in the membrane (p<0.001). Our results suggest that stimulation of TLR4 would induce the regulation of chemoattractant receptors which are key in the recruitment of leukocytes to the central nervous system and in the neuroinflammatory response. Further research is merited to delineate the precise mechanisms underlying this modulation and which consequences would have over this response.