Involvement of L-selectin expression in Burkholderia pseudomallei-infected monocytes invading the brain during murine melioidosis

Abstract

ABSTRACTThe 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.