To determine the number of BCG-mycobacteria in the mouse granulomas, we used the following two BCG counts.
Detection of granuloma macrophages with a large number of single BCG-mycobacteria, possibly in the cytoplasm of the host cells, raised the question as to how such host cells occur in mouse granulomas.
This allowed BCG-mycobacteria to survive and actively replicate in mouse granuloma cells.
However, the intracellular compartments where mycobacteria reside in mouse granuloma dendritic cells remain to be identified.
Our finding that ER stress is induced in macrophages residing in mouse and human lung granulomas during Mtb infection, notably where apoptotic cells accumulate, reveals a striking commonality to what we and others have observed in advanced atherosclerosis [9], [21], [40].
Tumor Necrosis Factor-alpha (TNFα) is required for the formation of protective granulomas during tuberculosis [30].
The combination of these events could therefore contribute to macrophage apoptosis in granulomas during TB infection.
The effect of AFN-1252 on gene expression in vivo was determined using a mouse subcutaneous granuloma infection model.
The concordance suggests that mice without granulomas may have been free from P. acnes in the normal indigenous flora of their lungs before and during the experiment.
Like µMT and JHD mice, the granuloma pathology of OBF-1-null mice was comparable to that of littermate control mice at eight weeks post-infection [8] [11].
