Effect of Mycobacterium tuberculosis-derived sulfolipid I on human phagocytic cells

Abstract

Experiments were performed to determine the effects of Mycobacterium tuberculosis-derived sulfolipid I on phagocytic cells. Sulfolipid I was taken up in significant amounts by human neutrophils and in lesser amounts by monocytes and lymphocytes. Superoxide (O2-) production by neutrophils was significantly increased by sulfolipid I, but the rate of production was slower than that reported previously for other stimuli. The optimal concentration of sulfolipid I for stimulation of O2- production was 27 micrograms/ml, while higher concentrations produced less. At substimulatory levels sulfolipid I caused enhancement of O2- release from neutrophils when it was subsequently stimulated by other agents. Nonadherent monocytes from most normal donors failed to produce O2- when treated with sulfolipid I; however, adherent monocytes pretreated with gamma interferon did produce O2- with sulfolipid I stimulation. Priming for an enhanced oxidative response of activated monocytes was also observed. These sulfolipid I-induced changes in phagocytic cell function may be important in altering the ability of phagocytes to respond effectively to M. tuberculosis and may also cause exaggerated inflammatory responses.

Down‐Regulatory Effect of Mycobacterium leprae Cell Wall Lipids on Phagocytosis, Oxidative Respiratory Burst and Tumour Cell Killing by Mouse Bone Marrow Derived Macrophages

“…These results are relevant considering that polar and particularly phospholipids are currently described in the literature as inhibitory substances for macrophages and T cell functions [6,8,10,11,18,20,34,35,38].…”

“…It has been reported in the literature that Mycobacteria antigens [15,34,35], and specifically ML antigens [5], inhibit superoxide production by macrophages. Our data clearly confirm these observations considering that ML or LE deeply suppressed O 2 production by BMD macrophages.…”

Mycobacterial virulence factors

“…Mycobacterial sulpholipid also has been considered as a virulence determinant. Sulpholipid is toxic to phagocytes and it has been suggested as contributing to inflammation by stimulation of the oxidative activity of phagocytes at sublethal concentrations (Zhang et al 1988) and responsible for the inhibition of phagosome-lysosome fusion by M y c o . tuberculosis by virtue of its polyanionic nature (Goren et al 1976).…”

A novel mutation alters the stability of PapA2 resulting in the complete abrogation of sulfolipids in clinical mycobacterial strains

“…Sulfolipids represent Mtb specific lipids that have been the focus of research over the last several years (18–20). The presence of sulfolipids has been classically associated with virulence of mycobacteria (21–24). Moreover, recent evidence has further corroborated their role in bacterial physiology.…”