divergent effects of mycobacterial cell wall glycolipids on maturation and function of human monocyte-derived dendritic cells不同分枝杆菌细胞壁的影响糖脂在人类monocyte-derived树突状细胞的成熟和功能.pdfVIP

Divergent Effects of Mycobacterial Cell Wall Glycolipids on Maturation and Function of Human Monocyte- Derived Dendritic Cells 1 1 2 2 2 Jolanta Mazurek , Lech Ignatowicz , Gunilla Kallenius , Stefan B. Svenson , Andrzej Pawlowski , Beston Hamasur2* ¨ 1 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden, 2 Department of Clinical Science and Education, Sodersjukhuset, Karolinska Institutet, Stockholm, Sweden Abstract Background: Mycobacterium tuberculosis (Mtb) is able to evade the immune defenses and may persist for years, decades and even lifelong in the infected host. Mtb cell wall components may contribute to such persistence by modulating several pivotal types of immune cells. Dendritic cells (DCs) are the most potent antigen-presenting cells and hence play a crucial role in the initial immune response to infections by connecting the innate with the adaptive immune system. Principal Findings: We investigated the effects of two of the major mycobacterial cell wall-associated types of glycolipids, mannose-capped lipoarabinomannan (ManLAM) and phosphatidylinositol mannosides (PIMs) purified from the Mtb strains H37Rv and Mycobacterium bovis, on the maturation and cytokine profiles of immature human monocyte-derived DCs. ManLAM from Mtb H37Rv stimulated the release of pro-inflammatory cytokines TNF, IL-12, and IL-6 and expression of co- stimulatory (CD80, CD86) and antigen-presenting molecules (MHC class II). ManLAM from M. bovis also induced TNF, IL-12 and IL-6 but at significantly lower levels. Importantly, whil