Leishmania infection modulates beta-1 integrin activation and alters the kinetics of monocyte spreading over fibronectin

Abstract

Contact with Leishmania leads to a decreases in mononuclear phagocyte adherence to connective tissue. In this work, we studied the early stages of bond formation between VLA 4 and fibronectin, measured the kinetics of membrane alignment and the monocyte cytoplasm spreading area over a fibronectin-coated surface, and studied the expression of high affinity integrin epitope in uninfected and Leishmania-infected human monocytes. Our results show that the initial VLA 4 -mediated interaction of Leishmania-infected monocyte with a fibronectin-coated surface is preserved, however, the later stage, leukocyte spreading over the substrate is abrogated in Leishmania-infected cells. The median of spreading area was 72 [55-89]μm 2 for uninfected and 41 [34-51]μm 2 for Leishmania-infected monocyte. This cytoplasm spread was inhibited using an anti-VLA 4 blocking antibody. After the initial contact with the fibronectrin-coated surface, uninfected monocyte quickly spread the cytoplasm at a 15μm 2 s -1 ratio whilst Leishmania-infected monocytes only made small contacts at a 5.5μm 2 s -1 ratio. The expression of high affinity epitope by VLA 4 (from 39 ± 21% to 14 ± 3%); and LFA1 (from 37 ± 32% to 18 ± 16%) molecules was reduced in Leishmania-infected monocytes. These changes in phagocyte function may be important for parasite dissemination and distribution of lesions in leishmaniasis.