Trogocytosis-associated cell to cell spread of intracellular bacterial pathogens
| Autor: | Sharon Taft-Benz, Lauren C. Radlinski, Jason Brunton, Shaun Steele, Thomas H. Kawula |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Cytoplasm cell to cell spread Immunological Synapses Mouse Cell Cell Communication Mice 0302 clinical medicine Biology (General) Microbiology and Infectious Disease biology General Neuroscience Salmonella enterica General Medicine 3. Good health medicine.anatomical_structure Medicine Insight Intracellular Research Article Cell signaling Trogocytosis Intracellular Bacteria QH301-705.5 Science Immunology General Biochemistry Genetics and Molecular Biology Microbiology Cell Line 03 medical and health sciences Immune system medicine Humans Animals trogocytosis Francisella tularensis General Immunology and Microbiology Intracellular parasite Macrophages Epithelial Cells biochemical phenomena metabolism and nutrition biology.organism_classification 030104 developmental biology Cell culture francisella tularensis Other salmonella typhimurium 030215 immunology |
| Zdroj: | eLife eLife, Vol 5 (2016) |
| ISSN: | 2050-084X |
| Popis: | Macrophages are myeloid-derived phagocytic cells and one of the first immune cell types to respond to microbial infections. However, a number of bacterial pathogens are resistant to the antimicrobial activities of macrophages and can grow within these cells. Macrophages have other immune surveillance roles including the acquisition of cytosolic components from multiple types of cells. We hypothesized that intracellular pathogens that can replicate within macrophages could also exploit cytosolic transfer to facilitate bacterial spread. We found that viable Francisella tularensis, as well as Salmonella enterica bacteria transferred from infected cells to uninfected macrophages along with other cytosolic material through a transient, contact dependent mechanism. Bacterial transfer occurred when the host cells exchanged plasma membrane proteins and cytosol via a trogocytosis related process leaving both donor and recipient cells intact and viable. Trogocytosis was strongly associated with infection in mice, suggesting that direct bacterial transfer occurs by this process in vivo. DOI: http://dx.doi.org/10.7554/eLife.10625.001 eLife digest Many of the bacteria that are able to cause disease in humans and other animals are able to grow inside their host’s cells. In doing so, these bacteria can avoid being recognized and killed by the host’s immune system. However, the ability of the bacteria to grow within the cell is constrained by the limited space and nutrients that are available inside the infected cell. The current theory is that most of these bacteria eventually kill the cell they have infected and are released into the body so that they can infect other host cells. However, since some host cells can exchange material with their neighbors, it is also possible that the bacteria may be able to travel directly between host cells without leaving the safety of the cell environment. Macrophages are immune cells that patrol the body to identify and destroy damaged host cells, bacteria and other microbes. Macrophages are also able to interact with neighboring healthy cells through a process called trogocytosis (“trogo” is essentially Greek for nibble). During this process, the membranes of the two participating cells briefly fuse and some of the proteins in the membranes are transferred from one cell to the other. Afterwards, the two cells separate but retain the membrane proteins they acquired from the other cell. The purpose of trogocytosis is poorly understood, but it is thought to help the host to develop immune responses against microbes and tumors. Steele et al. investigated whether infected mouse and human cells can transfer bacteria to healthy macrophages during trogocytosis. The experiments show that two types of bacteria – called Francisella tularensis and Salmonella enterica – can transfer from infected cells to macrophages via trogocytosis. Furthermore, the cells of mice infected with F. tularensis were more likely to undergo trogocytosis, which suggests that the bacterium may promote and use this process to spread throughout tissues in the body. Together, Steele et al.’s finding show that some bacteria can hijack a naturally occurring cellular process to move between host cells without re-entering the space that surrounds cells, or damaging either the donor or recipient cell.The next steps following on from this work are to find out how much trogocytosis contributes to the spread and progression of disease. A future goal is to understand the molecular mechanism of trogocytosis so it may be possible to develop drugs that can inhibit the spread of the bacteria in patients. DOI: http://dx.doi.org/10.7554/eLife.10625.002 |
| Databáze: | OpenAIRE |
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