Open AccessC andida albicans stimulates in vivo differentiation of haematopoietic stem and progenitor cells towards macrophages by a TLR2 ‐dependent signalling
Author(s) -
Megías Javier,
Maneu Victoria,
Salvador Pedro,
Gozalbo Daniel,
Gil M. Luisa
Publication year - 2013
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12104
Subject(s) - biology , tlr2 , haematopoiesis , progenitor cell , candida albicans , in vivo , transplantation , bone marrow , stem cell , immunology , toll like receptor , innate immune system , corpus albicans , microbiology and biotechnology , immune system , medicine
Summary T oll‐like receptors ( TLRs ) are expressed by haematopoietic stem and progenitor cells ( HSPCs ), and may play a role in haematopoiesis in response to pathogens during infection. We have previously demonstrated that (i) inactivated yeasts of C andida albicans induce in vitro differentiation of HSPCs towards the myeloid lineage, and (ii) soluble TLR agonists induce in vivo their differentiation towards macrophages. In this work, using an in vivo model of HSPCs transplantation, we report for the first time that HSPCs sense C . albicans in vivo and subsequently are directed to produce macrophages by a TLR2 ‐dependent signalling. Purified lineage‐negative cells ( L in − ) from bone marrow of C57BL /6 mice ( CD 45.2 alloantigen) were transplanted into B6Ly5.1 mice ( CD 45.1 alloantigen), which were then injected with viable or inactivated C . albicans yeasts. Transplanted cells were detected in the spleen and in the bone marrow of recipient mice, and they differentiate preferentially to macrophages, both in response to infection or in response to inactivated yeasts. The generation of macrophages was dependent on TLR2 but independent of TLR4 , as transplanted L in − cells from TLR2 −/− mice did not give rise to macrophages, whereas L in − cells from TLR4 −/− mice generated macrophages similarly to control cells. Interestingly, the absence of TLR2 , or in a minor extent TLR4 , gives L in − cells an advantage in transplantation assays, as increases the percentage of transplanted recovered cells. Our results indicatethat TLR ‐mediated recognition of C . albicans by HSPCs may help replace and/or increase cells that constitute the first line of defence against the fungus, and suggest that TLR ‐mediated signalling may lead to reprogramming early progenitors to rapidly replenishing the innate immune system and generate the most necessary mature cells to deal with the pathogen.