Kupffer cells restricts Mycobacterium tuberculosis growth better than alveolar macrophages

Abstract

Abstract Kupffer cells protect liver from bacterial infections. In the current study, we compared Mycobacterium tuberculosis (M.tb) growth and cytokine production by mice kupffer cells and alveolar macrophages. M.tb H37Rv infected kupffer cells and alveolar macrophages produced equal amounts of TNF-α, IL-6, IL-10 & IL-1β. In contrast, kupffer cells restricted M.tb growth better than alveolar macrophages (1 ± 0.346×106 CFU vs. 4 ± 0.916×106 CFU, p<0.03). There is no significant difference in the apoptosis of M.tb infected kupffer cells and alveolar macrophages. In contrast, M.tb infected kupffer cells expressed significant higher amounts of autophagy molecules LC-3B, ATG-7, ATG-5 and Beclin-1 (p<0.005, p<0.002, p<0.0032 & p<0.004 respectively) compared to M.tb infected alveolar macrophages as determined by real-time PCR. This was confirmed by Western blot and confocal microscopy. Our results suggest autophagy is involved in better restriction of M.tb growth by kupffer cells. Prime PCR analysis for 35 intracelluar signaling molecules those are involved in autophagy as well as in cytoskeleton indicated that M.tb infected kupffer cells significantly express higher levels of VASP (Vasodilator-stimulated phosphoprotein), RhoA (Ras homolog gene family member A) and Arp3 (Actin–related protein 3) genes (two fold, p<0.01, p<0.02&p<0.02 respectively) compared to M.tb infected alveolar macrophages. Studies are underway 1. To confirm whether autophagy is involved in better restriction of M.tb growth in kupffer cells. 2. Determine the role of cytoskeleton proteins those are involved in enhanced autophagy and M.tb growth inhibition in kupffer cells. 3. Determining in vivo relevance to our current findings using mouse model of M.tb infection.