title: Toll-like receptor 4-linked Janus kinase 2 signaling contributes to internalization of Brucella abortus by macrophages.
abstract: Brucella abortus is an intracellular pathogen that uses a crafty strategy to invade and proliferate within host cells, but the distinct signaling pathways associated with phagocytic mechanisms of B. abortus remain unclear. The present study was performed to test the hypothesis that Toll-like receptor 4 (TLR4)-linked signaling interacting with Janus kinase 2 (JAK2) plays an essential role in B. abortus phagocytosis by macrophages. The effects of TLR4-JAK2 signaling on B. abortus phagocytosis in murine macrophage RAW 264.7 cells were observed through an infection assay and confocal microscopy. We determined that the uptake of B. abortus was negatively affected by the dysfunction of TLR4 and JAK2. F-actin polymerization detected by flow cytometry and F-actin assay was amplified for B. abortus entry, whereas that event was attenuated by the disruption of TLR4 and JAK2. Importantly, JAK2 phosphorylation and actin skeleton reorganization were suppressed immediately after B. abortus infection in bone marrow-derived macrophages (BMDMs) from TLR4(-/-) mice, showing the cooperation of JAK2 with TLR4. Furthermore, small GTPase Cdc42 participated in the intermediate pathway of TLR4-JAK2 signaling on B. abortus phagocytosis. Consequently, TLR4-associated JAK2 activation in the early cellular signaling events plays a pivotal role in B. abortus-induced phagocytic processes in macrophages, implying the pathogenic significance of JAK2-mediated entry. Here, we elucidate that this specific phagocytic mechanism of B. abortus might provide achievable strategies for inhibiting B. abortus invasion.
authors: College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea.
authors: Jin Ju
authors: JJ
authors: Lee
authors: Dong Hyeok
authors: DH
authors: Kim
authors: Dae Geun
authors: DG
authors: Kim
authors: Hu Jang
authors: HJ
authors: Lee
authors: Wongi
authors: W
authors: Min
authors: Man Hee
authors: MH
authors: Rhee
authors: Jae Youl
authors: JY
authors: Cho
authors: Masahisa
authors: M
authors: Watarai
authors: Suk
authors: S
authors: Kim
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D002003:Brucella abortus / Q000378:metabolism* / Q000472:pathogenicity; D002006:Brucellosis / Q000378:metabolism / Q000382:microbiology; D002460:Cell Line; D004789:Enzyme Activation; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology / Q000382:microbiology*; D051379:Mice; D008809:Mice, Inbred C3H; D018613:Microscopy, Confocal; D010587:Phagocytosis; D058105:Polymerization; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; C581598:Cdc42 protein, mouse; D034741:RNA, Small Interfering; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D020764:cdc42 GTP-Binding Protein
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