Characterization of Endoplasmic Reticulum Stress and Apoptosis in Macrophages Infected with Mycobacterium tuberculosis Isolates from Korea Patients

Apoptosis is an important host defense mechanism against mycobacterial infection. Recent reports suggest that links between apoptosis and endoplasmic reticulum (ER) stress are critical for the regulation of mycobacterial survival; however, the exact regulatory mechanisms are not well known. In this study, we isolated 20 Mycobacterium tuberculosis (Mtb) clinical strains from Korean patients and examined ER stress-mediated apoptosis in Mtb-infected macrophages. Most Mtb strains increased the rates of apoptosis and production of ER stress-sensing molecules in mouse macrophages, similar to Mtb H37Rv infection. Moreover, the intracellular survival of Mtb clinical isolates in macrophages was similar to that of H37Rv. Our data suggest that infection with Mtb downregulated MCP-1 and MCPIP. The regulation of MCPIP may decrease ROS production, leading to a reduction in ER stress-mediated apoptosis.

Macrophage Polarization and Infection

Monocytes and macrophages regulate host immune system against infectious pathogens. Activated macrophages play an important role in restricting the multiplication and dissemination of pathogens. The concept of alternative activation of macrophages might provide useful insights into pathology of infectious diseases. M1 macrophages (classically activated macrophages) and M2 macrophages (alternatively activated macrophages) are associated with responses to tissue remodeling, pro-inflammatory and anti-inflammatory reactions in various infectious diseases. However, the relevance of macrophage polarization in several infectious diseases was not revealed clearly. Macrophage plasticity and polarization should be considered as a useful conceptual framework for understanding the unknown pathogenesis of infectious diseases. Here we reviewed the recent progress on macrophage polarization and its characters in infectious diseases.

The Synergistic Effects of Antimicrobial Peptides on the Growth Inhibition of Salmonella Typhimurium through Imd Pathway in Drosophila Intestine

Some Bacillus species present in fermented foods are regarded as probiotics because of their ability to modulate the prevention of some intestinal infections and the modulation of the inflammatory immune response. We isolated bacteriocin-like substances producing Bacillus subtilis and B. lentus from Cheonggukjang, a traditional Korean fermented soybean paste having an inhibitory effect against Salmonella Typhimurium using a well diffusion inhibition assay and a broth co-culturing method. B. subtilis or B. letus was fed to Drosophila melanogaster alone as well as in combination with Salmonella Typhimurium and survival was monitored daily. The survival rates by oral feeding B. subtilis, B. lentus and Salmonella Typhimurium separately resulted in 85, 90 and 75%, respectively. In contrast, survival rates of co-feeding of B. lentus with Salmonella Typhimurium were increased from 75 to 90% during 7 days post-feeding as compared to Salmonella Typhimurium alone. However, B. subtilis in co-feeding with Salmonella Typhimurium significantly reduced D. melanogaster survival rate (85 to 70%). We found that the immune response to B. lentus and Salmonella Typhimurium is characterized synergistic activation of antimicrobial peptide gene expression by Imd pathway. In conclusion, the in vitro and natural-route infection of the D. melanogaster digestive system can result in the use of the probiotic B. lentus for effective treatment of Salmonella Typhimurium infection. We therefore propose the strain B. lentus as a suitable candidate probiotics for use in the prevention and treatment of the intestinal infections caused by Salmonella Typhimurium.