Mycobacterium bovis BCG inhibits spontaneous apoptosis in human monocytes via a phosphatidylinositol (PI)-3 kinase dependent pathway

Mycobacterium attachment and uptake into monocytes has previously been shown to involve Protein Tyrosine Kinase (PTK), mitogen activated protein kinase (MAPK) and phosphatidylinositol (PI)-3 kinase pathways. Human monocytes were infected with BCG Copenhagen vaccine strain and host cell apoptosis was monitored over a time course using Annexin-V staining of cells. Monocytes were pretreated with pharmacological inhibitors to PTK, MAPK and PI-3 kinase pathways to investigate their role in BCG-induced apoptosis. BCG infection of monocytes increased within 24 h of stimulation at infection doses of 0.5, 1 and 2 per cell. BCG-induced inhibition of monocyte apoptosis was not affected by PTK inhibitor genistein (10 and 40 μM) or the MAPK inhibitor PD98059 (10 and 40 μM). However, when cells were pretreated with the PI 3-kinase inhibitor LY25009 (25 μM) BCG-induced monocyte survival was no longer observed. Our results suggest a role for the PI-3 kinase pathway in BCG-induced monocyte survival.