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The transcriptional profile of Langhans-like multinucleated giant macrophages: Collapse of the inflammatory and immune responses

ABSTRACT: Monocytes/macrophages have the ability to fuse in multinucleated giant cells (MGCs). Except for osteoclasts that resorb bones on large surfaces, the function of other macrophage-derived MGCs, which appear under pathological situations associated with granulomatous inflammation such as tuberculosis, is not understood. Here we deciphered functions and gene expression profiles of MGCs obtained after stimulation of human monocytes with IFN-g and concanavalin A. First, we show that the competence of MGCs in phagocytosis and O2- production was similar to those of monocytes-derived macrophages (MDMs) and that MGCs exhibited a M1 polarization. Second, we analyzed the transcriptional profile of MGCs using gene categories and the building of gene networks. The signature of MGCs was markedly distinct from that of resting or stimulated MDMs. It consisted of the up-regulation of genes involved in adhesion and cytoskeleton organization while genes associated with immune response were down-regulated. Hence, MGC formation was associated with a profound and original modulation of gene expression repertoire suggesting that macrophage immune were not prominent in MGC. This expression gene repertoire may be instrumental to understand the specific function of this giant macrophages in human pathologies

ORGANISM(S): Homo sapiens

PROVIDER: GSE30273 | GEO | 2012/12/07

SECONDARY ACCESSION(S): PRJNA143737

REPOSITORIES: GEO

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Project description:A major population of placenta macrophages represented throughout the pregnancy consists of CD14+ macrophages, but their characteristics remain badly understood. Here we purified from placentas at term CD14+ macrophages using positive selection. The phenotyping of CD14+ macrophages performed using flow cytometry revealed that placenta CD14+ macrophages expressed a series of markers distinct of those of circulating monocytes monocyte-derived macrophages. Placenta CD14+ macrophages spontaneously matured in multinucleated giant cells (MGCs) as demonstrated by size, number of nuclei display and specific cytoskeleton organization. Placenta CD14+ macrophages and MGCs were phagocytic cells but the potential of MGCs to mount an inflammatory response was lower than that of their precursors. Placenta CD14+ macrophages and MGCs stimulated with interferon and interleukin-4 were not polarized into typical M1 or M2 profiles. Placenta macrophages exhibited specific activation transcriptional programs. Indeed, principal component analysis and hierarchical clustering show that placental macrophages formed a distinct group from circulating monocytes and monocyte-derived macrophages. Among placenta macrophages, it was also possible to distinguish CD14+ macrophages and MGCs. In addition, networks based on gene interactions were clearly different in CD14+ macrophages and MGCs. Finally, the microenvironment of placenta CD14+ macrophages governs their differentiation into MGCs because CD14+ macrophages incubated with trophoblasts exhibited exarcerbated characteristics of MGCs and because the co-incubation of circulating monocytes from working women with trophoblast supernatants resulted into the formation of MGCs whereas monocytes from non-pregnant women incubated with trophoblast supernatants did not differentiate into MGCs. Taken together, these results clearly demonstrated specific feaures of placenta CD14+ macrophages. Three replicates of each of the following: 1. Placental macrophages just after isolation (CD14+ macrophages) 2. Placental macrophages after 9 days in culture (MGCs) 3. CD14+ cells isolated from PBMC which are extracted from the whole human blood of healthy donors (Monocytes) 4. Macrophages derived from monocytes (MDMs)

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The transcriptional profile of Langhans-like multinucleated giant macrophages: Collapse of the inflammatory and immune responses

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