Of Men Not Mice: Bactericidal/Permeability-Increasing Protein Expressed in Human Macrophages Acts as a Phagocytic Receptor and Modulates Entry and Replication of Gram-Negative Bacteria.
Macrophages as immune cells prevent the spreading of pathogens by means of active phagocytosis and killing. We report here the presence of an antimicrobial protein, bactericidal/permeability-increasing protein (BPI) in human macrophages, which actively participates in engulfment and killing of Gram-negative pathogens. Our studies revealed increased expression of BPI in human macrophages during bacterial infection and upon stimulation with various pathogen-associated molecular patterns,viz., LPS and flagellin. Furthermore, during the course of an infection, BPI interacted with Gram-negative bacteria, resulting in enhanced phagocytosis and subsequent control of the bacterial replication. However, it was observed that bacteria which can maintain an active replicating niche (SalmonellaTyphimurium) avoid the interaction with BPI during later stages of infection. On the other hand,Salmonellamutants, which cannot maintain a replicating niche, as well asShigella flexneri, which quit the endosomal vesicle, showed interaction with BPI. These results propose an active role of BPI in Gram-negative bacterial clearance by human macrophages.
Department of Microbiology and Cell Biology, Indian Institute of Science , Bangalore , India.
Arjun
A
Balakrishnan
Institute for Immunology, University of Marburg , Marburg , Germany.
Markus
M
Schnare
Centre for Biosystems Science and Engineering, Indian Institute of Science , Bangalore , India.
Dipshikha
D
Chakravortty
Gram-negative bacteria; antimicrobial protein; bacterial niche; innate immunity; macrophage evolution; phagocytic receptor