The effect of Mtb aggregation on monocyte-derived macrophage transcription profiles

Mycobacterium tuberculosis (Mtb) bacilli readily aggregate. We previously reported that Mtb aggregates lead to phagocyte death and subsequent efficient replication in the dead infected cells. Here we examined the transcriptional response of human monocyte derived macrophages to phagocytosis of aggregated Mtb relative to phagocytosis of non-aggregated single or multiple bacilli. Infection with aggregated Mtb led to an early upregulation of pro-inflammatory associated genes and enhanced TNF-alpha signaling via the NFkappaB pathway. These pathways were significantly more highly upregulated relative to infection with single or multiple non-aggregated bacilli per cell. Overall design: We infected monocyte derived macrophages with single, multiple non-aggregated and multiple aggregated Mtb bacilli (3 repeats for each of 4 infection conditions from 5 donors). Total number of samples = 60, including 15 uninfected controls.