Some pathogenic strains of bacteria defy host defense systems by invading immune cells and disarming them. In new work published in the June issue of Nature Immunology, researchers show Brucella bacteria have devised a new way to survive inside potently deadly host immune cells.
Brucella avoid being killed inside their host by making a sugary-like substance called cyclic beta-1,2-glucans (C beta G). Macrophages -- large white blood cells that target infection -- typically envelop bacteria by surrounding them with a membrane coat, creating a pouch full of bacteria, which is internalized and directed to specialized killing zones called lysosomes. Gorvel and colleagues show C beta G interferes with patches found on the host membranes, known as lipid rafts, that are somehow required for this process. This activity of C beta G blocks fusion of lysosomes with the bacterial-laden pouches. Mutant bacteria that cannot make C beta G are killed inside the macrophage lysosomes. Importantly, Brucella themselves do not rapidly kill their host cells. By making C beta G, Brucella can survive for long periods as parasites living inside the infected macrophages.
Brucella are commonly associated with livestock diseases, many times responsible for causing spontaneous abortion in cattle, horses, dogs and sheep. However, Brucella can cause disease in humans (for example Malta fever) whose livelihoods involve close contact with animals. Thus, the new work identifies an important molecule to target against Brucella infections in both humans and animals.
Jean-Pierre Gorvel (CNRS, Centre d'Immunologie Parc scientifique de Luminy, Marseille, France)
Additional contact for comment on the paper:
Craig Roy (Yale University, New Haven, CT)
Online publication can be accessed by clicking here.
(C) Nature Immunology press release.
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