Host membrane glycosphingolipids and lipid microdomains facilitate Histoplasma capsulatum internalization by macrophages.

AbstractRecognition and internalization of intracellular pathogens by host cells is a multifactorial process, involving both stable and transient interactions. The plasticity of the host cell plasma membrane is fundamental in this infectious process. Here, the participation of macrophage lipid microdomains during adhesion and internalization of the fungal pathogenHistoplasma capsulatum (Hc) was investigated. An increase in membrane lateral organization, which is characteristic of lipid microdomains, was observed during the first steps of Hc ‐macrophage interaction. Cholesterol enrichment in macrophage membranes around Hc contact regions and reduced levels of Hc‐macrophage association after cholesterol removal also suggested the participation of lipid microdomains during Hc‐macrophage interaction. Using optical tweezers (OT) to st udy cell‐to‐cell interactions, we showed that cholesterol depletion increased the time required for Hc adhesion. Additionally, fungal internalization was significantly reduced under these conditions. Moreover, macrophages treated with the ceramide‐glucosyltransferase inhibitor (P4r) and macrop hages with altered ganglioside synthesis (fromB4galnt1 ( ‐/‐) mice) showed a deficient ability to interact with Hc. Co‐incubation of oligo‐GM1 and treatment with Cholera toxin subunit B, which recognizes the ganglioside GM1, also reduced Hc association. Although purified GM1 did not alter Hc binding, treatment with P4 significantly increased...
Source: Cellular Microbiology - Category: Microbiology Authors: Tags: RESEARCH ARTICLE Source Type: research