Bacterial immunostat: Mycobacterium tuberculosis lipids and their role in the host immune response

Abstract

The lipid-rich cell wall of Mycobacterium tuberculosis is a dynamic structure that is involved in the regulation of the transport of nutrients, toxic host-cell effector molecules, and anti-tuberculosis drugs. It is therefore postulated to contribute to the longterm bacterial survival in an infected human host. Accumulating evidence suggests that M. tuberculosis remodels the lipid composition of the cell wall as an adaptive mechanism against host-imposed stress. Some of these lipid species (trehalose dimycolate, diacylated sulphoglycolipid, and mannan-based lipoglycans) trigger an immunopathologic response, whereas others (phthiocerol dimycocerosate, mycolic acids, sulpholipid-1, and di-and polyacyltrehalose) appear to dampen the immune responses. These lipids appear to be coordinately expressed in the cell wall of M. tuberculosis during different phases of infection, ultimately determining the clinical fate of the infection. This review summarizes the current state of knowledge on the metabolism, transport, and homeostatic or immunostatic regulation of the cell wall lipids, and their orchestrated interaction with host immune responses that results in bacterial clearance, persistence, or tuberculosis.

Systematic Identification of Mycobacterium tuberculosis Effectors Reveals that BfrB Suppresses Innate Immunity

“…Compared with other fractions of Mtb, the membrane proteins and secreted proteins have higher potential to interact with macrophage proteins (49,50). Interestingly, of the 34 shared proteins (supplemental Fig.…”

The Lipid Virulence Factors of Mycobacterium tuberculosis Exert Multilayered Control over Autophagy-Related Pathways in Infected Human Macrophages

“…While quite a few mycobacterial proteins have been investigated, very little is known about the role of Mtb lipids in macrophage autophagy. In particular, little information is available on the noncovalently associated lipids located in the outermost part of the cell envelope, despite the fact that several of them contribute efficiently to pathogenesis [20,21].…”

Robust lysosomal rewiring in Mtb infected macrophages mediated by Mtb lipids restricts the intracellular bacterial survival

“…Mycobacterial components, including surface lipids and proteins, have been observed in the infected cells outside of the mycobacterial phagosome, as well as in neighboring non-infected cells (Aliprantis et al, 1999; Beatty et al, 2001; Beatty et al, 2000; Beatty and Russell, 2000; Dao et al, 2004; Fineran et al, 2017; Harth et al, 1994; Harth et al, 1996; Korf et al, 2005; Neyrolles et al, 2001; Queiroz and Riley, 2017; Sakamoto et al, 2013; Sequeira et al, 2014), where they can influence the antigen presenting capacity of macrophages or interfere with other macrophage functions (Russell et al, 2002). Specifically, individual mycobacterial lipids, including Phosphatidylinositol mono- and di mannosides (PIMs), phosphatidylglycerol, cardiolipin, phosphatidylethanolamine, trehalose mono- and dimycolates are released into the macrophage and accumulate in late endosomes/lysosomes (Beatty et al, 2001; Beatty et al, 2000; Beatty and Russell, 2000; Russell et al, 2002).…”