Human macrophages differentiated in the presence of vitamin D3 restrict dengue virus infection and innate responses by downregulating mannose receptor expression

Alzate, John F. Arboleda; Rodenhuis-Zybert, Izabela A.; Hernández, Juan Carlos; Smit, Jolanda M.; Urcuqui-Inchima, Silvio

doi:10.1371/journal.pntd.0005904

Cited by 52 publications

(78 citation statements)

References 56 publications

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“…A recent study determined that M2 macrophages displayed slightly higher phagocytic activity than M1 cells, and phagocytosis was not changed by treatment with 1,25(OH) 2 D 3 (36). Furthermore, MDMs treated with low-dose 1,25(OH) 2 D 3 for 6 days were less infected with dengue virus compared with untreated MDMs, which was proposed to be due to reduced viral uptake via CD206 that was down-regulated on 1,25(OH) 2 D 3 -tretated MDMs (37). In contrast, we found that CD206 was upregulated on Mtb-infected monocyte-derived cells that were polarized with a higher dose of 1,25(OH) 2 D 3 the last 20 h of 6 days differentiation.…”

Section: Discussionmentioning

confidence: 91%

Polarization of Human Monocyte-Derived Cells With Vitamin D Promotes Control of Mycobacterium tuberculosis Infection

et al. 2020

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Background: Understanding macrophage behavior is key to decipher Mycobacterium tuberculosis (Mtb) pathogenesis. We studied the phenotype and ability of human monocyte-derived cells polarized with active vitamin D [1,25(OH) 2 D 3 ] to control intracellular Mtb infection compared with polarization of conventional subsets, classical M1 or alternative M2. Methods: Human blood-derived monocytes were treated with active vitamin D or different cytokines to obtain 1,25(OH) 2 D 3-polarized as well as M1-and M2-like cells or fully polarized M1 and M2 subsets. We used an in vitro macrophage Mtb infection model to assess both phenotype and functional markers i.e., inhibitory and scavenger receptors, costimulatory molecules, cytokines, chemokines, and effector molecules using flow cytometry and quantitative mRNA analysis. Intracellular uptake of bacilli and Mtb growth was monitored using flow cytometry and colony forming units. Results: Uninfected M1 subsets typically expressed higher levels of CCR7, TLR2, and CD86, while M2 subsets expressed higher CD163, CD200R, and CD206. Most of the investigated markers were up-regulated in all subsets after Mtb infection, generating a mixed M1/M2 phenotype, while the expression of CD206, HLADR, and CD80 was specifically up-regulated (P < 0.05) on 1,25(OH) 2 D 3-polarized macrophages. Consistent with the pro-inflammatory features of M1 cells, Mtb uptake and intracellular Mtb growth was significantly (P < 0.01-0.001 and P < 0.05-0.01) lower in the M1 (19.3%) compared with the M2 (82.7%) subsets 4 h post-infection. However, infectivity rapidly and gradually increased in M1 cells at 24-72 h. 1,25(OH) 2 D 3-polarized monocyte-derived cells was the most potent subset to inhibit Mtb growth at both 4 and 72 h (P < 0.05-0.01) post-Mtb infection. This ability was associated with high mRNA levels of pro-inflammatory cytokines and the antimicrobial peptide LL-37 but also anti-inflammatory IL-10, while expression of the immunosuppressive enzyme IDO (indoleamine 2,3-dioxygenase) remained low in Mtb-infected 1,25(OH) 2 D 3-polarized cells compared with the other subsets. Rao Muvva et al. Vitamin D-Mediated Macrophage Polarization in Tuberculosis Conclusions: Mtb infection promoted a mixed M1/M2 macrophage activation, and 1,25(OH) 2 D 3-polarized monocyte-derived cells expressing LL-37 but not IDO, were most effective to control intracellular Mtb growth. Macrophage polarization in the presence of vitamin D may provide the capacity to mount an antimicrobial response against Mtb and simultaneously prevent expression of inhibitory molecules that could accelerate local immunosuppression in the microenvironment of infected tissue.

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Section: Discussionmentioning

confidence: 91%

Polarization of Human Monocyte-Derived Cells With Vitamin D Promotes Control of Mycobacterium tuberculosis Infection

et al. 2020

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“…DENV infection was evaluated in PBMCs by the intracellular detection of the viral E protein using the murine monoclonal anti-flavivirus 4G2 antibody (clone D1-4G2-4-15; Millipore, Darmstadt, Germany, IgG2a) for 25 min and the respective secondary anti-mouse IgG2a-PE (Jackson ImmunoResearch, West Grove, PA) antibody for an additional 25 min at 4°in the dark. 16 These incubations were completed after the panel staining (see above), in which none of the antibodies were IgG2. For intracellular staining, PBMCs were fixed and permeabilized as discussed previously.…”

Section: Detection Of the Viral E Proteinmentioning

confidence: 99%

Different phenotypes of non‐classical monocytes associated with systemic inflammation, endothelial alteration and hepatic compromise in patients with dengue

et al. 2018

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Summary Although dengue can progress to severe stages, the exact causes of this phenomenon are unknown; however, the possibility of monocyte participation is acknowledged. It has been suggested that monocyte subsets (classical, intermediate and non‐classical) play differential roles in dengue immunopathology. Therefore, we determined the count of monocyte subsets and obtained the clinical information of patients with dengue. We noted a significant decrease in the count of non‐classical monocytes in patients compared with controls. With this finding, we focused on studying the phenotype of non‐classical monocytes in the present study. An increase in activation and differentiation markers, such as CD64, CD86, the percentage of tumor necrosis factor‐α+ cells and exposure of phosphatidylserine, were recorded in the non‐classical monocytes of patients compared with controls. Moreover, a significant decrease in the expression of CX3CR1 with a corresponding increase in the expressions of CCR2, CCR5, CD11b and CD54 was detected in the non‐classical monocytes of patients in comparison with that of the controls. Significant increases in the frequency of microparticles from endothelium and in the concentrations of interleukin‐6 (IL‐6), IL‐8 and IL‐10 were noted in the plasma of patients. These findings demonstrate that in patients with dengue, non‐classical monocytes are activated, exhibiting a phenotype associated with more differentiation, produces tumor necrosis factor‐α and has a profile of less endothelial surveillance closer to the cellular migration. These changes were associated with hepatic compromise, endothelial alteration and high concentration of circulating cytokines. Hence, alterations of non‐classical monocytes seem to be associated with the immunopathology of dengue infection.

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“…Los niveles séricos de IL-1β e IL-6 se cuantificaron por el método Enzyme-Linked ImmunoSorbent Assay (ELISA) usando un estuche comercial específico para cada citoquina (BD Biosciences, Franklin Lakes, NJ), y siguiendo las instrucciones previamente reportadas (15) . Los resultados se leyeron a una longitud de onda de 450 nm y se reportaron en pg/ml.…”

Section: Cuantificación De Il-1β E Il-6unclassified

Modulación de los niveles de lipoproteínas de alta densidad y las citoquinas IL-1β e IL-6 en pacientes con dengue

Barrientos-Arenas

Henao-García

Giraldo

et al. 2018

Rev Peru Med Exp Salud Publica

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Objetivos. Evaluar los niveles de lipoproteínas de alta densidad (HDL) y citoquinas proinflamatorias en pacientes con dengue clasificados según la gravedad del cuadro clínico. Materiales y métodos. Se realizó un estudio descriptivo, incluyendo 70 individuos con dengue, clasificados como: sin signos de alarma (DSSA), con signos de alarma (DCSA) y dengue grave (DG); 15 donantes sanos fueron incluidos como controles (CS). Los niveles séricos de IL-1β e IL-6 fueron cuantificados por ELISA, y los de HDL en suero por ensayo colorimétrico; además se determinó el recuento de plaquetas y el porcentaje de hematocrito. Resultados. Los niveles de IL-1β e IL-6 se encontraron aumentados en los pacientes con DENV respecto a los controles sanos. Dicho aumento fue más evidente en los pacientes con dengue, de acuerdo con la gravedad del cuadro clínico. Los niveles de HDL se hallaron disminuidos en los pacientes con dengue comparados con los controles sanos. Los análisis de correlación mostraron asociaciones estadísticamente significativas entre HDL y el número de plaquetas; así como entre el porcentaje de hematocrito y los niveles de IL-1β. Conclusiones. El aumento de IL-1β e IL-6 y la disminución de HDL en los estadios clínicos más graves sugieren que ambos factores están implicados en el desarrollo de la patogénesis y severidad. Las correlaciones permiten observar una posible asociación entre HDL y el número de plaquetas que permite dar una aproximación al posible papel de las HDL en la patogénesis del dengue, pero aún es necesario realizar estudios adicionales que permitan elucidar su importancia en el curso de la infección por DENV.

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Human macrophages differentiated in the presence of vitamin D3 restrict dengue virus infection and innate responses by downregulating mannose receptor expression

Cited by 52 publications

References 56 publications

Polarization of Human Monocyte-Derived Cells With Vitamin D Promotes Control of Mycobacterium tuberculosis Infection

Polarization of Human Monocyte-Derived Cells With Vitamin D Promotes Control of Mycobacterium tuberculosis Infection

Different phenotypes of non‐classical monocytes associated with systemic inflammation, endothelial alteration and hepatic compromise in patients with dengue

Modulación de los niveles de lipoproteínas de alta densidad y las citoquinas IL-1β e IL-6 en pacientes con dengue

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