candida albicans induces selective development of macrophages and monocyte derived dendritic cells by a tlr2 dependent signalling白色念珠菌诱导选择性发展巨噬细胞和单核细胞的树突细胞tlr2相关的信号.pdfVIP

Candida albicans Induces Selective Development of Macrophages and Monocyte Derived Dendritic Cells by a TLR2 Dependent Signalling ´ ˜ 1 ´ 2 ´ 2 1 1 Alberto Yanez , Javier Megıas , Jose-Enrique O’Connor , Daniel Gozalbo , M. Luisa Gil * ´ ´ ` ´ ´ 1 Departamento de Microbiologıa y Ecologıa, Universitat de Valencia, Burjassot, Spain, 2 Laboratorio de Citomica, Unidad Mixta CIPF-UVEG, Centro de Investigacion ´ ‘‘Prıncipe Felipe’’, Valencia, Spain Abstract As TLRs are expressed by haematopoietic stem and progenitor cells (HSPCs), these receptors may play a role in haematopoiesis in response to pathogens during infection. We have previously demonstrated that in in vitro defined conditions inactivated yeasts and hyphae of Candida albicans induce HSPCs proliferation and differentiation towards the myeloid lineage by a TLR2/MyD88 dependent pathway. In this work, we showed that C. albicans invasive infection with a low virulence strain results in a rapid expansion of HSPCs (identified as LKS cells: Lin2 c-Kit+ Sca-1+ IL-7Ra2), that reach the maximum at day 3 post-infection. This in vivo expansion of LKS cells in TLR22/ 2 mice was delayed until day 7 post- infection. Candidiasis was, as expected, accompanied by an increase in granulopoiesis and decreased lymphopoiesis in the bone marrow. These changes were more pronounced in TLR22/ 2 mice correlating with their higher fungal burden. Accordingly, emigration of Ly6Chigh monocyt