Pathogen associated molecular pattern-decorated mesoporous silica-A colloidal model for studying bacterial-host cell interactions.

Abstract

Tuberculosis is the top infectious disease worldwide and the development of a vaccine and diagnostic tools to control the disease is a priority that requires a better understanding of the factors involved in the pathogenesis of Mycobacterium tuberculosis, the infectious agent. It is known that bacterial cell surface components are released, interact with immune cell receptors, and may traffic toward host cell structures. Many of these compounds are lipids that have been associated with mycobacterial virulence. However, their hydrophobic nature has frequently hampered their biological study. In this work, silica particles were coated with functional lipids to obtain a colloidal bioinspired system based on nonhydrosoluble glycolipids. Mycobacterium tuberculosis phosphatidylinositol mannosides (PIMs), known to interact with receptors of innate immune cells, were purified from the M. tuberculosis H37Rv type strain, and used to prepare large unilamellar liposomes in combination with zwitterionic phosphatidyl choline. Then, bacillary-like Santa Barbara Amorphous-15 (SBA-15) silica particles were cationized and the vesicle fusion method was used to promote the attachment of anionic PIM-containing lipid bilayers. Thermogravimetric analysis, x-ray diffraction, N2 adsorption-desorption isotherm analysis, Fourier transform infrared spectroscopy, electron microscopy, and zeta potential analyses were used to characterize the materials obtained. The as-prepared PIM-containing colloids, named PIM@SBA-15, showed biocompatibility toward human fibroblasts and were found to colocalize with Toll-like receptor (TLR)2 upon their incubation with THP1-derived macrophages. Furthermore, the particles induced the formation of pseudopods and were internalized into phagocytic cells. In all, these data suggest the usefulness of PIM@SBA-15 particles to better comprehend the interactions between immune cells and PIMs.