Hijacking of macrophages by Salmonella (3,10:r:-) through 'types-III' secretion-like exocytotic signalling: a mechanism for infection of chicken ileum.
ABSTRACT Ultrastructual studies of experimentally infected chicken (n=5) ileum reveal that virulent Salmonella (3,10:r:-) signal their own phagocytosis by tissue macrophages, and are able to dodge host defence mechanisms. The observed fusion of membrane vesicles (MVs) liberated from virulent organisms with closely interacting macrophages is proposed here to constitute a mechanism of type III secretion-like system of gram-negative organisms in general, in order to translocate the necessary biochemical signals into the cytosol of macrophages (eukaryotic host cells). This leads to (1) membrane ruffling culminating in augmented phagocytosis of salmonellae, (2) inhibition of phagosome-lysosome (P-L) fusion for survival and replication of pathogens within the host cytoplasm and (3) initiation of apoptosis of the infected macrophages and ultimate release of replicated salmonellae from the migrating host cells.
Full-textDOI: · Available from: Rakesh Yashroy, Jul 01, 2015
- SourceAvailable from: Rakesh YashroyInternational Symposium on "Salmonella and Salmonellosis"; 05/2002
- Toxicology International 01/2003; 10(1):1-9.
- [Show abstract] [Hide abstract]
ABSTRACT: Originally isolated from severe human food-poisoning cases, Salmonella (3,10:r:-), a monophasic variety of otherwise diphasic serotypes such as S. weltevreden and S. simi, causes serious infections in man, animals and poultry. Mechanism of infection of this versatile and deadly organism is important to understand for its control. The objective of this study was to enhance our understanding of infection of Salmonella (3,10:r:-) in vivo at cellular level. Aliquots of 10(9) cfu of Salmonella (3,10:r:-) organisms were injected intra-ileally in 24 h pre-fasted 3 month old broiler chickens by standard ligated ileal loop method. After 18 h, the fluid accumulated in the ileum was drained and small tissue pieces were fixed in 2.5 per cent buffered (pH 7) glutaraldehyde and subsequently in 1 per cent aqueous osmium tetraoxide. Ultra-thin sections of araldite-embedded tissue pieces were examined under transmission electron microscope operated at 100 KV after staining with uranyl acetate and lead citrate. Over 70 per cent of salmonellae interacting within 300 nm with ileal epithelial cells developed numerous surface blebs of periplasmic extensions designated "periplasmic organelles" (POs). Large sized POs were apparently pinched off as outer membrane vesicles (OMVs), 50-90 nm in diameter. Type III secretion needle complex-like "rivet complexes" (RCs) were viewed to rivet the bacterial outer and inner membranes together, allowing only pockets of periplasm to expand/inflate in order to liberate OMVs. Many OMVs were found visibly docked on the plasma membrane of host epithelial cells. The invading organisms appeared to leave the epithelial cells so as to find entry into the lymphatic vessels, where, they again appeared to be closely interacting with ileal macrophages, by forming numerous POs and concomitantly liberating OMVs. Inside the cytoplasm of macrophages, numerous tight phagosomes were seen, each containing two organisms. The final stage appeared to contain replicated salmonellae, four in each loose phagosome and, at the same time, macrophages also showed signs of apoptotic disintegration, culminating in the release of replicated salmonellae. Outer membrane vesicles released from a fiercely virulent human isolate, Salmonella 3,10:r:- pathogens have been implicated in translocating biochemical signals from the host-interactive organisms to the eukaryotic cells at both stages of invasion leading to epithelial cell and macrophage infection in vivo, in the chicken ileal model. A comprehensive cellular mechanism at ultrastructural level is outlined for typhoid-like Salmonella infections caused by this humans-infecting organism.The Indian Journal of Medical Research 01/2008; 126(6):558-66.
Questions & Answers about this publication
- Can 'clever' bacterial pathogens exploit host defence in their own favour like in this paper here? Host defence mechanisms are to stop pathogens to infect and spread disease, but can that be exploited by the invading pathogens?Following