Liver macrophages controls Mycobacterium tuberculosis growth by enhancing autophagy

Abstract

Abstract Alveolar macrophages are the first cells to come in contact with TB pathogen in lung, but unable to eliminate Mycobacterium tuberculosis (M. tb) completely and serves as niche. In the current study, we compared M. tb growth and cytokine production by murine alveolar and liver macrophages. We found three-fold higher CFU in alveolar macrophages compared to liver macrophages (5 ± 1.7 × 106 vs. 1.776 ± 0.5 ×106 CFU) indicating that liver macrophages are more efficient in inhibiting M. tb growth. In contrast, M. tb H37Rv infected alveolar and liver macrophages produced equal amounts of TNF-α, IL-6, IL-10 & IL-1β. There is no significant difference in the apoptosis and M1/M2 paradigm of M. tb infected alveolar and liver macrophages. Flow cytometry analysis revealed the percentage of LC-3B+ M. tb infected liver macrophages were two-fold higher compared to percentage of LC-3B+ M. tb infected alveolar macrophage. This was confirmed by real time PCR. We also noted distinctly enhanced LC-3B puncta formation in infected liver macrophages as examined by confocal microscopy. We found significantly enhanced M. tb CFU in liver macrophages transfected with LC-3B, ATG-5, ATG-7 and Beclin-1 siRNA compared to liver macrophages transfected with control siRNA (p<0.01; 0.006; 0.01&0.002) respectively. Our results suggest that autophagy is involved in better restriction of M. tb growth by liver macrophages. Studies are underway to compare metabolic changes of control and M. tb H37Rv infected alveolar and liver macrophages and in vivo relevance to our current findings using mouse model of M. tb infection.