Activation of neutrophils by mycobacteria and mycobacterial components

Abstract

The genus Mycobacterium includes free-living saprophytes, opportunists, and human pathogens.Mycobacterium tuberculosis, the organism causing tuberculosis, as well as other pathogenicmycobacteria can survive and multiply inside phagocytic cells, but the underlying mechanisms areonly partly understood. The innate immune response to mycobacterial infections is predominantlymediated and regulated by activated macrophages. Neutrophils are, however, an important part of thefirst-line of defence against most microorganisms. Protection is achieved either by direct killing of thebacteria or through production of cytokines. The neutrophils might therefor be important also in thedefence against mycobacteria.The aim of this study was to investigate the neutrophil responses induced by cell wall componentsand whole cells representing mycobacteria that differ concerning virulence. The study was focused onthe capability of mycobacterial cell wall structures or whole mycobacteria cells to induce an oxidativeresponse and production of cytokines.Phenolic glycolipids (PGLs) from M. kansasii and M. tuberculosis induced an oxidative responsein human neutrophils, which PGLs from M. marinum and M. bovis BCG were unable to do. Thecarbohydrate part was shown to be of crucial importance for the interaction. In contrast, the cell wallcomponent lipoarabinomannan (LAM) was unable to bring about a significant oxidative response inneutrophils, but induced a primed state in the cells. The primed state was accompanied by granulemobilisation, shown as an increased exposure of receptors as well as a release of granule contents.Neutrophils were also exposed to whole living mycobacterial cells and it was shown that M.tuberculosis, the opportunistic M. avium, and the non-pathogenic M. smegmatis all induced aproduction/release of TNF-a, IL-6, and IL-8 from human neutrophils. The amounts induced by M.tuberculosis were, however, lower than for the other non-pathogenic bacteria. The inefficientinduction of these cytokines in neutrophils could be a mechanism for the tubercle bacilli to persist,while the non-pathogenic mycobacteria are effectively eliminated.In conclusion, mycobacteria and mycobacterial components do affects neutrophils. The oxygenradicals produced and the cytokines released might be important parts in the early defence againstmycobacterial infections.