Processing of mycobacterial lipids and effects on host responsiveness

Abstract

One of the most important opportunistic pathogens associated with AIDS is the Mycobacterium avium complex. M. avium infections are found in up to 70% of individuals in advanced stages of AIDS. The deficiency in our knowledge of these mycobacteria presents an obstacle to the development of a rational approach for controlling these life-threatening infections in immunocompromised persons. It is apparent that M. avium can replicate in host macrophages and persist for long periods. During this time, various components, particularly lipids, accumulate in host macrophages and contribute to the ability of this organism to upset the cytokine homeostasis necessary for controlling infections of this type. M. avium lipids are immunosuppressive and can induce a variety of cytokines and eicosanoids that affect general host responses. The intention of this review is to examine the postphagocytic processing of various M. avium lipids with respect to their ability to alter host responses, particularly in immunocompromised patients such as those infected with HIV.

Mycobacterial Lysocardiolipin Is Exported from Phagosomes upon Cleavage of Cardiolipin by a Macrophage-Derived Lysosomal Phospholipase A2

“…By using purified lipids, we could demonstrate that intact M can degrade major mycobacterial lipids such as PIM 4 and mycoside B, and that this leads to the integration of radioactivity into M lipids such as phosphatidylinositol, phosphatidylethanolamine, and phosphatidylglycerol (data not shown). This observation is in contrast to earlier statements claiming that mycobacterial lipids are highly resistant to degradation by the host cell (23).…”

Bacteriology: Review paratuberculosis: How doesmycobacterium aviumsubsp.Paratuberculosisresist intracellular degradation?

“…The mycobacterial envelope consists of four layers: from inside out, the plasma membrane, electron-dense layer, electron-transparent layer, and outer layer (7,68). The plasma membrane, like that of other bacteria, is composed of a lipid bilayer with embedded membrane proteins.…”

“…Lipoarabinomannan is found in all the three layers of the cell wall. Other components of the cell wall include phosphatidylinositol mannosides, lipoproteins, cord factor (a-a-D-trehalose 6, 6'-dimycolate), macrophage inhibitory factor (MIF-A3), and other glycolipids (7,15,66,78).…”

“…It suppresses macrophage activation and T-cell stimulation, and scavenges potentially cytotoxic substances (7,18,83). The peptidoglycanarabinogalactan complex is responsible for the adjuvancity and induction of tumor necrosis factor (TNF) release.…”

“…When M. avium grows inside macrophages, they accumulate within the phagosomal/phagolysosomal compartment and appear as a peribacillary space or an electron-transparent zone surrounding the bacteria on transmission electron microscopy ( Figure lb) (7). This electron-transparent capsule surrounding the mycobacteria may serve as a passive barrier and protect the pathogen from toxic and enzymatic attack.…”