Synthetic Lipopeptide MALP-2 Inhibits Intracellular Growth of Mycobacterium bovis BCG in Alveolar Macrophages—Preliminary Data

Abstract

Alveolar macrophages (AM) are the primary target cell of the lung for inhaled mycobacterial pathogens. We investigated the effect of the synthetic lipopeptide MALP-2 on the interaction between AM from rats and Mycobacterium bovis BCG. AM were infected with M. bovis BCG at a multiplicity of infection (MOI) of 10 and then cultured in medium alone or medium supplemented with either synthetic macrophage activating lipopeptide-2 (MALP-2), or IFN-gamma, or both. Mycobacterial CFU were counted on days 3 and 7 and cell-free supernatants were collected for cytokine measurements. Treatment of macrophages with MALP-2 led to reduced bacterial loads by day 3 and 7 post-infection and at the same time enhanced the release of TNF-alpha, IL-6 und IL-10 compared to non-stimulated, M. bovis BCG-infected AM. Macrophages co-treated with MALP-2 and IFN-gamma or IFN-gamma in the absence of MALP-2 limited the growth of M. bovis BCG only by day 3, but not day 7 post-stimulation. Our data show that MALP-2 is effective in decreasing bacterial loads in lung sentinel cells.

The Influence of Macrophage-Activating Lipopeptide 2 (MALP-2) on Local and Systemic Inflammatory Response in a Murine Two-Hit Model of Hemorrhagic Shock and Subsequent Sepsis

“…Also, results from Zeckey et al from a murine sepsis model might support a protective role of MALP-2 for lung tissue. While the significantly reduced levels of IL-6, TNF-α, and MIP-1α in the alveolar tissue found at the end of the observation period (96 h) might be interpreted as a residual pulmonary response on the one hand [10], Jörgens et al showed that local IL-10 in the lung was significantly increased after pre-treatment of alveolar macrophages with MALP-2 [21] on the other hand. Thus, local pre-treatment with MALP-2 might beneficially influence the lung against inflammation by elevated antiinflammatory IL-10 concentrations and lowered proinflammatory mediator levels.…”