Dataset Information

NF-kappaB and phosphatidylinositol 3-kinase activity mediates the HCMV-induced atypical M1/M2 polarization of monocytes.

ABSTRACT: Human cytomegalovirus infection of monocytes stimulates a unique monocyte differentiation reprogramming resulting in polarization towards an M1 pro-inflammatory macrophage that simultaneously exhibits characteristics of an M2 anti-inflammatory macrophage. Our laboratory has previously shown that HCMV infection stimulates monocyte NF-kappaB and PI(3)K activities and now provides evidence that these cellular factors are essential for the HCMV-induced polarization of infected monocytes/macrophages. We find that the induction of NF-kappaB and PI(3)K activities following HCMV infection was required for the initiation of monocyte-to-macrophage differentiation. HCMV-infected monocytes treated with Bay11-7802 (an inhibitor of NF-kappaB activity) or LY294002 [an inhibitor of PI(3)K activity] prior to infection exhibited a small, round and monocyte-like undifferentiated morphology and the lack of CD68 upregulation (a macrophage differentiation marker). Detailed transcriptome analysis revealed 48%, 7% and 31% of HCMV-induced M1-associated genes were dependent on NF-kappaB, PI(3)K or both activities, respectively; while 100% of HCMV-induced M2-associated genes required both NF-kappaB and PI(3)K activities. Functionally, we demonstrated that NF-kappaB and PI(3)K activities were critical for the production of M1- and M2-associated cytokines/chemokines, in HCMV-induced differentiating monocytes. Supernatant from HCMV-infected monocytes pretreated with Bay11-7802 or LY294002 exhibited an 80% and 67% reduction in cell motility-inducing activity. Overall, these data show that HCMV usurps monocyte NF-kappaB and PI(3)K signal transduction pathways to induce the unique polarization of HCMV-infected monocytes needed for the earliest steps in the viral dissemination and persistence strategy.

SUBMITTER: Chan G

PROVIDER: S-EPMC2736317 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

NF-kappaB and phosphatidylinositol 3-kinase activity mediates the HCMV-induced atypical M1/M2 polarization of monocytes.

Chan Gary G Bivins-Smith Elizabeth R ER Smith M Shane MS Yurochko Andrew D AD

Virus research 20090507 1-2

Human cytomegalovirus infection of monocytes stimulates a unique monocyte differentiation reprogramming resulting in polarization towards an M1 pro-inflammatory macrophage that simultaneously exhibits characteristics of an M2 anti-inflammatory macrophage. Our laboratory has previously shown that HCMV infection stimulates monocyte NF-kappaB and PI(3)K activities and now provides evidence that these cellular factors are essential for the HCMV-induced polarization of infected monocytes/macrophages. ...[more]

PMID: 19427341

Similar Datasets

Project description:Macrophages belong to a special phagocytic subgroup of human leukocytes and are one of the important cells of the human immune system. Small noncoding RNAs are a group of small RNA molecules that can be transcribed without the ability to encode proteins but could play a specific function in cells. SncRNAs mainly include microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs) and repeat RNAs. We used high-throughput sequencing analysis and qPCR to detect the expression changes of the small noncoding RNAome during macrophage polarization. Our results showed that 84 miRNAs and 47 miRNAs with were downregulated during M1 macrophage polarization and that 11 miRNAs were upregulated and 19 miRNAs were downregulated during M2 macrophage polarization. MiR-novel-3-nature and miR-27b-5p could promote expression of TNF-α which was marker gene of M1 macrophages. The piRNA analysis results showed that 69 piRNAs were upregulated and 61 piRNAs were downregulated during M1 macrophage polarization and that 3 piRNAs were upregulated and 10 piRNAs were downregulated during M2 macrophage polarization. DQ551351 and DQ551308 could promote the mRNA expression of TNF-α and DQ551351overexpression promoted the antitumor activity of M1 macrophages. SnoRNA results showed that 62 snoRNAs were upregulated and 59 snoRNAs were downregulated during M1 macrophage polarization, whereas 6 snoRNAs were upregulated and 10 snoRNAs were downregulated during M2 macrophage polarization. Overexpression of snoRNA ENSMUST00000158683.2 could inhibit expression of TNF-α. For snRNA, we found that 12 snRNAs were upregulated and 15 snRNAs were downregulated during M1 macrophage polarization and that 2 snRNAs were upregulated during M2 macrophage polarization. ENSMUSG00000096786 could promote expression of IL-1 and iNOS and ENSMUSG00000096786 overexpression promoted the antitumor activity of M1 macrophages. Analysis of repeat RNAs showed that 7 repeat RNAs were upregulated and 9 repeat RNAs were downregulated during M1 macrophage polarization and that 2 repeat RNAs were downregulated during M2 macrophage polarization. We first reported the expression changes of piRNA, snoRNA, snRNA and repeat RNA during macrophage polarization, and preliminarily confirmed that piRNA, snoRNA and snRNA can regulate the function of macrophages.

Dataset Information

NF-kappaB and phosphatidylinositol 3-kinase activity mediates the HCMV-induced atypical M1/M2 polarization of monocytes.

Publications

NF-kappaB and phosphatidylinositol 3-kinase activity mediates the HCMV-induced atypical M1/M2 polarization of monocytes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets