title: Involvement of L-selectin expression in Burkholderia pseudomallei-infected monocytes invading the brain during murine melioidosis.
abstract: The development of neurologic melioidosis was linked to the elicitation of Burkholderia pseudomallei-infected L-selectinhiCD11b+BALB/c cells in our previous study. However, whether monocytic L-selectin (CD62L, encoded by the sell gene) is a key factor remains uncertain. In the present study, after establishing multi-organ foci via hematogenous routes, we demonstrated that B. pseudomallei GFP steadily persisted in blood, splenic, hepatic and bone marrow (BM) Ly6C monocytes; however, the circulating CD16/32+CD45hiGFP+brain-infiltrating leukocytes (BILs) derived from the blood Ly6C monocytes were expanded in BALB/c but not in C57BL/6 bacteremic melioidosis. Consistent with these results, 60% of BALB/c mice but only 10% of C57BL/6 mice exhibited neurologic melioidosis. In a time-dependent manner, B. pseudomallei invaded C57BL/6 BM-derived phagocytes and monocytic progenitors by 2 d. The number of Ly6C+CD62L+GFP+inflamed cells that had expanded in the BM and that were ready for emigration peaked on d 21 post-infection. Hematogenous B. pseudomallei-loaded sell+/+Ly6C monocytes exacerbated the bacterial loads and the proportion of Ly6C+GFP+BILs in the recipient brains compared to sell-/-infected Ly6C cells when adoptively transferred. Moreover, a neutralizing anti-CD62L antibody significantly depleted the bacterial colonization of the brain following adoptive transfer of B. pseudomallei-loaded C57BL/6 or BALB/c Ly6C cells. Our data thus suggest that Ly6C+CD62L+infected monocytes served as a Trojan horse across the cerebral endothelium to induce brain infection. Therefore, CD62L should be considered as not only a temporally elicited antigen but also a disease-relevant leukocyte marker during the development of neurologic melioidosis.
authors.affiliation: a Department of Internal Medicine , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.|b Department of Internal Medicine , National Yang-Ming University , Taipei , Taiwan.
authors.forename: Yao-Shen
authors.initials: YS
authors.lastname: Chen
authors.affiliation: c Section of Infectious Disease , Department of Medicine , E-Da Hospital and University , Kaohsiung Taiwan.
authors.forename: Hsi-Hsun
authors.initials: HH
authors.lastname: Lin
authors.affiliation: d Department of Biological Science , National Sun Yat-sen University , Kaohsiung , Taiwan.|e Department of Biotechnology , National Kaohsiung Normal University , Kaohsiung , Taiwan.
authors.forename: Pei-Tan
authors.initials: PT
authors.lastname: Hsueh
authors.affiliation: e Department of Biotechnology , National Kaohsiung Normal University , Kaohsiung , Taiwan.
authors.forename: Wei-Fen
authors.initials: WF
authors.lastname: Ni
authors.affiliation: e Department of Biotechnology , National Kaohsiung Normal University , Kaohsiung , Taiwan.
authors.forename: Pei-Ju
authors.initials: PJ
authors.lastname: Liu
authors.affiliation: f Department of Public Health , College of Health Science, Kaohsiung Medical University , Kaohsiung , Taiwan.|g Institute of Environmental Engineering, National Sun Yat-sen University , Kaohsiung , Taiwan.
authors.forename: Pei-Shih
authors.initials: PS
authors.lastname: Chen
authors.affiliation: h Department of Molecular Biology and Human Genetics , Tzu Chi University , Hualien , Taiwan.
authors.forename: Hsin-Hou
authors.initials: HH
authors.lastname: Chang
authors.affiliation: h Department of Molecular Biology and Human Genetics , Tzu Chi University , Hualien , Taiwan.
authors.forename: Der-Shan
authors.initials: DS
authors.lastname: Sun
authors.affiliation: e Department of Biotechnology , National Kaohsiung Normal University , Kaohsiung , Taiwan.
authors.forename: Ya-Lei
authors.identifier: 0000-0003-0893-955X
authors.initials: YL
authors.lastname: Chen
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics; D001921:Brain / Q000382:microbiology*; D016957:Burkholderia pseudomallei / Q000472:pathogenicity* / Q000502:physiology; D004195:Disease Models, Animal; D019041:L-Selectin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008554:Melioidosis / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000382:microbiology*; D009422:Nervous System Diseases / Q000382:microbiology
chemical_list: D000950:Antigens, Ly; C494192:Ly-6C antigen, mouse; D019041:L-Selectin
keywords: Burkholderia pseudomallei; L-selectin; Ly6C+CD62L+; Trojan horse; neurologic melioidosis