CD16+ and CD16− human blood monocyte subsets differentiate in vitro to dendritic cells with different abilities to stimulate CD4+ T cells

Sánchez-Torres, Carmen; García-Romo, Gina Stella; Cornejo-Cortés, Miguel A.; Rivas-Carvalho, Amaranta; Sánchez-Schmitz, Guzman

doi:10.1093/intimm/13.12.1571

Cited by 146 publications

(161 citation statements)

References 40 publications

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“…In agreement with our results, it has been described that LPS-matured CD16 + Mo-DCs secreted low amounts of IL-12 [27], suggesting that CD16 + Mo-DCs could represent an important population of regulatory DCs [28]. We also showed that matured CD16 + Mo-DCs displayed low levels of IL-1β production while IL-10 or TNF-α production did not differed between subsets.…”

Section: Discussionsupporting

confidence: 92%

“…Regarding CD1 molecules expression, it has been established that CD1a expression is lower on DCs derived from CD16 + Mos than from CD16 − Mos [27,28], which is in agreement with our results. Nevertheless, it has been reported that CD16 + Mos are more prone to differentiate into DCs [27,38,39], which is in contrast to our results and to the extensive literature that associates CD16 + Mos with a M -like phenotype [40][41][42]. In fact, human CD16 + Mos were phenotypically related to pulmonary alveolar M s and some authors have speculated a commitment of these circulating Mos to migrate to the lung [40].…”

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confidence: 93%

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Impaired dendritic cell differentiation of CD16‐positive monocytes in tuberculosis: Role of p38 MAPK

et al. 2013

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Tuberculosis (TB) is one of the world's most pernicious diseases mainly due to immune evasion strategies displayed by its causative agent Mycobacterium tuberculosis (Mtb). Blood monocytes (Mos) represent an important source of DCs during chronic infections; consequently, the alteration of their differentiation constitutes an escape mechanism leading to mycobacterial persistence. We evaluated whether the CD16 + /CD16 − Mo ratio could be associated with the impaired Mo differentiation into DCs found in TB patients. The phenotype and ability to stimulate Mtb-specific memory clones DCs from isolated Mo subsets were assessed. We found that CD16 − Mos differentiated into CD1a + DC-SIGN high cells achieving an efficient recall response, while CD16 + Mos differentiated into a CD1a − DC-SIGN low population characterized by a poor mycobacterial Ag-presenting capacity. The high and sustained phosphorylated p38 expression observed in CD16 + Mos was involved in the altered DC profile given that its blockage restored DC phenotype and its activation impaired CD16 − Mo differentiation. Furthermore, depletion of CD16 + Mos indeed improved the differentiation of Mos from TB patients toward CD1a + DC-SIGN high DCs. Therefore, Mos from TB patients are less prone to differentiate into DCs due to their increased proportion of CD16 + Mos, suggesting that during Mtb infection Mo subsets may have different fates after entering the lungs. Keywords: Dendritic cells r Monocyte differentiation r Tuberculosis See accompanying Commentary by Lugo-Villarino and NeyrollesAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionMonocytes (Mos) are large circulating leukocytes of the myeloid lineage that mediate essential functions of innate immunity including phagocytosis and cytokine production [1,2]. Mos are produced Correspondence: Dr. Luciana Balboa e-mail: luciana_balboa@hotmail.com in the bone marrow and released into the blood, and circulate in blood or reside in a spleen reservoir and, upon tissue infiltration they can differentiate into macrophages (M s) or DCs. Although human blood Mos are a highly heterogeneous population, two main subsets have been described: CD14 + CD16 − "classical" Mos are the major Mo population and CD14 + CD16 + Mos, the minor one (5-10% of total Mos). The latter subset has a more mature phenotype and an enhanced proinflammatory activity [3]. This heterogeneity has led to the hypothesis that Mos are committed to specific functions prior to tissue infiltration [4]. Also, C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 336Luciana Balboa et al. Eur. J. Immunol. 2013. 43: 335-347 an imbalance in the relative proportions of the subsets during acute inflammation [5] and several infectious diseases [6][7][8][9][10] including tuberculosis (TB) [11,12] has been described. TB, a disease that mainly affects the respiratory system, infects onethird of the world's population and kills 2 million people each year [13]. The success o...

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Section: Discussionsupporting

confidence: 92%

supporting

confidence: 93%

Impaired dendritic cell differentiation of CD16‐positive monocytes in tuberculosis: Role of p38 MAPK

et al. 2013

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“…Hence, macrophages with a "resident" phenotype may also exert proinflammatory functions. Both resident and inflammatory monocyte subsets can differentiate into DCs in vitro by the addition of IL-4 and GM-CSF [28,29]. An additional, though smaller, third population of blood monocytes was described in humans.…”

Section: Heterogeneity Of the Mononuclear Phagocyte Systemmentioning

confidence: 99%

Intestinal macrophages: differentiation and involvement in intestinal immunopathologies

2009

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Intestinal macrophages, preferentially located in the subepithelial lamina propria, represent the largest pool of tissue macrophages in humans. As an adaptation to the local antigen-and bacteria-rich environment, intestinal macrophages exhibit several distinct phenotypic and functional characteristics. Notably, microbe-associated molecular pattern receptors, including the lipopolysaccharide (LPS) receptors CD14 and TLR4, and also the Fc receptors for IgA and IgG are absent on most intestinal macrophages under homeostatic conditions. Moreover, while macrophages in the intestinal mucosa are refractory to the induction of proinflammatory cytokine secretion, they still display potent phagocytic activity. These adaptations allow intestinal macrophages to comply with their main task, i.e., the efficient removal of microbes while maintaining local tissue homeostasis. In this paper, we review recent findings on the functional differentiation of monocyte subsets into distinct macrophage populations and on the phenotypic and functional adaptations that have evolved in intestinal macrophages in response to their antigen-rich environment. Furthermore, the involvement of intestinal macrophages in the pathogenesis of celiac disease and inflammatory bowel diseases is discussed.

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“…The most popular model to study monocyte-derived DCs is to culture blood Mo of either subset 27 in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-4 5,28 or other related cytokine cocktails. 29 These DCs have been considered the 'gold standard' DC 30 for assessing maturation and many aspects of human DC biology.…”

Section: Introductionmentioning

confidence: 99%

Differential expression of the fractalkine chemokine receptor (CX3CR1) in human monocytes during differentiation

et al. 2014

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Circulating monocytes (Mos) may continuously repopulate macrophage (MAC) or dendritic cell (DC) populations to maintain homeostasis. MACs and DCs are specialized cells that play different and complementary immunological functions. Accordingly, they present distinct migratory properties. Specifically, whereas MACs largely remain in tissues, DCs are capable of migrating from peripheral tissues to lymphoid organs. The aim of this work was to analyze the expression of the fractalkine receptor (CX 3 CR1) during the monocytic differentiation process. Freshly isolated Mos express high levels of both CX 3 CR1 mRNA and protein. During the Mo differentiation process, CX 3 CR1 is downregulated in both DCs and MACs. However, MACs showed significantly higher CX 3 CR1 expression levels than did DC. We also observed an antagonistic CX 3 CR1 regulation by interferon (IFN)-c and interleukin (IL)-4 during MAC activation through the classical and alternative MAC pathways, respectively. IFN-c inhibited the loss of CX 3 CR1, but IL-4 induced it. Additionally, we demonstrated an association between CX 3 CR1 expression and apoptosis prevention by soluble fractalkine (sCX 3 CL1) in Mos, DCs and MACs. This is the first report demonstrating sequential and differential CX 3 CR1 modulation during Mo differentiation. Most importantly, we demonstrated a functional link between CX 3 CR1 expression and cell survival in the presence of sCX 3 CL1.

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CD16+ and CD16− human blood monocyte subsets differentiate in vitro to dendritic cells with different abilities to stimulate CD4+ T cells

Cited by 146 publications

References 40 publications

Impaired dendritic cell differentiation of CD16‐positive monocytes in tuberculosis: Role of p38 MAPK

Impaired dendritic cell differentiation of CD16‐positive monocytes in tuberculosis: Role of p38 MAPK

Intestinal macrophages: differentiation and involvement in intestinal immunopathologies

Differential expression of the fractalkine chemokine receptor (CX3CR1) in human monocytes during differentiation

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