Lipid metabolism and its implication in mycobacteria-host interaction

Abstract

The complex lipids present in the cell wall of Mycobacterium tuberculosis (Mtb) act as major effector molecules that actively interact with the host, modulating its metabolism and stimulating the immune response, which in turn affects the physiology of both, the host cell and the bacilli. Lipids from the host are also nutrient sources for the pathogen and define the fate of the infection by modulating lipid homeostasis. Although new technologies and experimental models of infection have greatly helped understanding the different aspects of the host-pathogen interactions at the lipid level, the impact of this interaction in the Mtb lipid regulation is still incipient, mainly because of the low background knowledge in this area of research.

Figure 1

Schematic representation of lipid biosynthesis pathways and their interactions in M. tuberculosis.

Figure 2

Role of the host-mycobacterial lipids interactions during macrophages infection. The cell envelope of mycobacteria comprise a wealth of unique glyco-lipids that act as PAMPs and are recognized by macrophages and DCs through PRRs such as Toll-like receptors (TLRs), Nod-like receptors (NLRs), and CLRs. In this scheme, we highlight the main host-mycobacterial lipid interactions and their consequences. Mtb lipids prevent the phagosome maturation, acidification and fusion with lysosomes; they also inhibit autophagy, in order to create a permissive niche that allows bacteria to resist degradation, and eventually replicate within the macrophage. During infection, macrophages accumulate lipids that can be used for Mtb as carbon and energy sources. Apa and LpqH: surface glyco- and lipoproteins, TACO/coronin 1: actin-binding host protein, Mincle: macrophage-inducible C-type lectin, RNS: reactive nitrogen species, MR: C-type lectins Mannose Receptor, DC-SIGN: dendritic cell-specific ICAM-grabbing non-integrin (only in DCs), CR3: complement receptor type 3, SIGNR3: DC-SIGN homologue in mice.