Azithromycin drives in vitro GM-CSF/IL-4-induced differentiation of human blood monocytes toward dendritic-like cells with regulatory properties

Abstract

Azithromycin, a macrolide antibacterial, has been shown to modify the phenotype of macrophages. We have investigated whether azithromycin in vitro is able to modulate the differentiation of human blood monocytes to DCs. iA-DCs appear to have a unique phenotype, characterized by increased granularity, adherence, and a surface molecule expression profile similar to that of MDCs, namely, CD1a -CD14 -CD71 ϩ CD209 high , as well as high CD86 and HLA-DR expression. The iA-DC phenotype is associated with increased IL-6 and IL-10 release, increased CCL2 and CCL18 expression and release, and M-CSF expression, as well as reduced CCL17 expression and release. Upon maturation with LPS, A-DCs and MDCs exhibit decreased expression of HLA-DR and costimulatory molecules, CD40 and CD83, as well as an increase in IL-10 and a decrease in CCL17 and CXCL11 secretion. These modulated responses of iA-DCs were associated with the ability to reduce a MLR, together with enhanced phagocytic and efferocytotic properties. Azithromycin, added 2 h before activation of iDCs with LPS, enhanced IL-10 release and inhibited IL-6, IL-12p40, CXCL10, CXCL11, and CCL22 release. In conclusion, azithromycin modulates the differentiation of blood monocyte-derived DCs to form iA-DCs with a distinct phenotype similar to that of iMDCs, accompanied by enhanced phagocytic and efferocytic capabilities. It also modifies LPS-induced DC maturation by decreasing surface molecule expression required for T cell activation, increasing IL-10 production, and inducing MLR-reducing properties. J. Leukoc. Biol. 91: 229 -243; 2012.

Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression

“…AZ is known to accumulate mainly in phagocytes, including resident macrophages and dendritic cells, which represent the major targets for the immunomodulatory effects of the drug [13] . Since AZ can drive the generation of the anti-inflammatory M2 macrophage phenotype, it is pertinent that it also promotes phagocytosis of hepatocyte debris and hepatic progenitor cell differentiation [13,44,47] . Given the strong accumulation of AZ in hepatocyte lysosomes, it may also directly inhibit hepatic cyto-and chemokine synthesis, as well as hepatocyte apoptosis [13,48] .…”

Myeloid-Derived Suppressor Cells Impair Alveolar Macrophages through PD-1 Receptor Ligation during Pneumocystis Pneumonia

“…Since the major component of zymosan beads is ␤-glucan, they resemble the cyst form of Pneumocystis. In addition, zymosan beads are commonly used as the substrate for phagocytosis assays (50)(51)(52). Each sample first was examined under a fluorescence microscope, and the number of zymosan beads phagocytosed by a total of 100 AMs was determined by confocal microscopy.…”

CXCL7-induced macrophage infiltration in lung tumor is independent of CXCR2 expression

“…To study the impact of CXCL7 protein on chemotactic activity of myeloid cells, recombinant form of the protein was used. The addition of recombinant CXCL7 protein significantly increased the chemotactic activity of neutrophils derived from C57BL/6 mouse bone marrow (by 40%, p < 0.05) and J774 macrophage cells (by 142%, p < 0.05) known as CD206 + [21,22] (Fig. 3).…”