Candida albicans stimulates in vivo differentiation of haematopoietic stem and progenitor cells towards macrophages by a TLR2-dependent signalling

Toll-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 Candida 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 (Lin−) from bone marrow of C57BL/6 mice (CD45.2 alloantigen) were transplanted into B6Ly5.1 mice (CD45.1 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 Lin− cells from TLR2−/− mice did not give rise to macrophages, whereas Lin− cells from TLR4−/− mice generated macrophages similarly to control cells. Interestingly, the absence of TLR2, or in a minor extent TLR4, gives Lin− 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.

A new boundary-based morphological model

Mathematical morphology addresses the problem of describing shapes in an n-dimensional space using the concepts of set theory. A series of standardized morphological operations are defined, and they are applied to the shapes to transform them using another shape called the structuring element. In an industrial environment, the process of manufacturing a piece is based on the manipulation of a primitive object via contact with a tool that transforms the object progressively to obtain the desired design. The analogy with the morphological operation of erosion is obvious. Nevertheless, few references about the relation between the morphological operations and the process of design and manufacturing can be found. The non-deterministic nature of classic mathematical morphology makes it very difficult to adapt their basic operations to the dynamics of concepts such as the ordered trajectory. A new geometric model is presented, inspired by the classic morphological paradigm, which can define objects and apply morphological operations that transform these objects. The model specializes in classic morphological operations, providing them with the determinism inherent in dynamic processes that require an order of application, as is the case for designing and manufacturing objects in professional computer-aided design and manufacturing (CAD/CAM) environments. The operators are boundary-based so that only the points in the frontier are handled. As a consequence, the process is more efficient and more suitable for use in CAD/CAM systems.