Mycobacterial_Lipoarabinomannan_negatively_modulates_macrophages_responses_Aspergillus_fumigatus_raw_data_raw_images

Mycobacterial virulence factors, like lipoarabinomannan, have been shown to interfere with host's intracellular pathways required for an effective immune response, however, the immunological basis for mycobacterial-fungal coinfection is still unknown. We therefore investigated the effect of lipoarabinomannan on macrophage responses against <i>Af</i>.Bone marrow-derived macrophages (BMDMs) were stimulated with non-mannose-capped lipoarabinomannan (LAM) from <i>Mycobacterium smegmatis</i> or mannose-capped lipoarabinomannan (ManLAM) from <i>Mycobacterium tuberculosis</i> for 2 hours and then infected with swollen <i>Af</i> conidia. Cell death was assessed by lactate dehydrogenase release. Cytokine release was measured in supernatant using Enzyme Linked Immuno-Sorbent Assay (ELISA). Colony forming units counting and time-lapse fluorescence microscopy was performed for studying conidia killing by macrophages.BMDMs stimulated with LAM showed increased cell death and inflammatory cytokine release in a dose-dependent manner, characterised by a significant increase of IL-1β release. Time-lapse fluorescence microscopy and CFUs revealed that both LAM and ManLAM significantly decrease the capacity of macrophages to kill <i>Af</i> conidia within the first 6 hours of infection.