NR AOHX

AU Watarai,M.; Kim,S.; Erdenebaatar,J.; Makino,S.; Horiuchi,M.; Shirahata,T.; Sakaguchi,S.; Katamine,S.

TI Cellular prion protein promotes Brucella infection into macrophages

QU Journal of Experimental Medicine 2003 Jul 7; 198(1): 5-17

PT journal article

AB The products of the Brucella abortus virB gene locus, which are highly similar to conjugative DNA transfer system, enable the bacterium to replicate within macrophage vacuoles. The replicative phagosome is thought to be established by the interaction of a substrate of the VirB complex with macrophages, although the substrate and its host cellular target have not yet been identified. We report here that Hsp60, a member of the GroEL family of chaperonins, of B. abortus is capable of interacting directly or indirectly with cellular prion protein (PrPc) on host cells. Aggregation of PrPc tail-like formation was observed during bacterial swimming internalization into macrophages and PrPc was selectively incorporated into macropinosomes containing B. abortus. Hsp60 reacted strongly with serum from human brucellosis patients and was exposed on the bacterial surface via a VirB complex-associated process. Under in vitro and in vivo conditions, Hsp60 of B. abortus bound to PrPc. Hsp60 of B. abortus, expressed on the surface of Lactococcus lactis, promoted the aggregation of PrPc but not PrPc tail formation on macrophages. The PrPc deficiency prevented swimming internalization and intracellular replication of B. abortus, with the result that phagosomes bearing the bacteria were targeted into the endocytic network. These results indicate that signal transduction induced by the interaction between bacterial Hsp60 and PrPc on macrophages contributes to the establishment of B. abortus infection.

MH Animal; Bacterial Proteins/*physiology; Brucella abortus/*physiology; Cells, Cultured; Chaperonin 60/*physiology; Female; Macrophages/*microbiology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Phenotype; Prions/*physiology; Proteins/physiology; Signal Transduction; Support, Non-U.S. Gov't

AD Department of Applied Veterinary Science, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro-shi, Hokkaido 080-8555, Japan. watarai@obihiro.ac.jp

SP englisch

PO USA

EA pdf-Datei

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