Lysophosphatidylcholine exacerbates Leishmania major-dendritic cell infection through interleukin-10 and a burst in arginase1 and indoleamine 2,3-dioxygenase activities.

ABSTRACT

Leishmania major is an obligate intracellular parasite hosted by phagocytes, including dendritic cells (DCs). Lysophosphatidylcholine (LPC) a pro-oxidant by-product of phospholipase A2 activity can modulate the maturation and function of DCs. However, little is known about its role in L. major infection. This study examined the effects of LPC and lipopolysaccharide (LPS) in BALB/c mouse-derived DC infection by L. major promastigotes, in vitro. Our results showed early divergent effects of LPS and LPC, which lasted up to 24h. In contrast to LPS, LPC worsened DC infection by reversing the immune balance IL-10 vs. TNF-α and IL-6, and inducing a sharp down regulation of CD40 and iNOsynthase activity. In addition, LPC potentiated xanthine oxidase stress, the production of kynurenine by indoleamine 2,3 dioxygenase (IDO), and arginase1 activity in the expense of iNOsynthase. Taken together, our results highlight some biochemical events bypassing the protective Th1 response. They suggest that LPC could facilitate the proliferation of this obligate intracellular parasite by neutralizing oxidative and nitrosative stresses and sustaining both IDO and arginase1 activities.