Delayed polarization of mononuclear phagocyte transcriptional program by type I interferon isoforms

BACKGROUND: Interferon (IFN)-α is considered a key modulator of immunopathological processes through a signature-specific activation of mononuclear phagocytes (MPs). This study utilized global transcript analysis to characterize the effects of the entire type I IFN family in comparison to a broad panel of other cytokines on MP previously exposed to Lipopolysaccharide (LPS) stimulation in vitro. RESULTS: Immature peripheral blood CD14+ MPs were stimulated with LPS and 1 hour later with 42 separate soluble factors including cytokines, chemokines, interleukins, growth factors and IFNs. Gene expression profiling of MPs was analyzed 4 and 9 hours after cytokine stimulation. Four hours after stimulation, the transcriptional analysis of MPs revealed two main classes of cytokines: one associated with the alternative and the other with the classical pathway of MP activation without a clear polarization of type I IFNs effects. In contrast, after 9 hours of stimulation most type I IFN isoforms induced a characteristic and unique transcriptional pattern separate from other cytokines. These "signature" IFNs included; IFN-β, IFN-α2b/α2, IFN-αI, IFN-α2, IFN-αC, IFN-αJ1, IFN-αH2, and INF-α4B and induced the over-expression of 44 genes, all of which had known functional relationships with IFN such as myxovirus resistance (Mx)-1, Mx-2, and interferon-induced hepatitis C-associated microtubular aggregation protein. A second group of type I IFNs segregated separately and in closer association with the type II IFN-γ. The phylogenetic relationship of amino acid sequences among type I IFNs did not explain their sub-classification, although differences at positions 94 through 109 and 175 through 189 were present between the signature and other IFNs. CONCLUSION: Seven IFN-α isoforms and IFN-β participate in the late phase polarization of MPs conditioned by LPS. This information broadens the previous view of the central role played by IFN-α in autoimmunity and tumor rejection by including and/or excluding an array of related factors likely to be heterogeneously expressed by distinct sub-populations of individuals in sickness or in response to biological therapy

Delayed polarization of mononuclear phagocyte transcriptional program by type I interferon isoforms

Abstract Background Interferon (IFN)-α is considered a key modulator of immunopathological processes through a signature-specific activation of mononuclear phagocytes (MPs). This study utilized global transcript analysis to characterize the effects of the entire type I IFN family in comparison to a broad panel of other cytokines on MP previously exposed to Lipopolysaccharide (LPS) stimulation in vitro. Results Immature peripheral blood CD14+ MPs were stimulated with LPS and 1 hour later with 42 separate soluble factors including cytokines, chemokines, interleukins, growth factors and IFNs. Gene expression profiling of MPs was analyzed 4 and 9 hours after cytokine stimulation. Four hours after stimulation, the transcriptional analysis of MPs revealed two main classes of cytokines: one associated with the alternative and the other with the classical pathway of MP activation without a clear polarization of type I IFNs effects. In contrast, after 9 hours of stimulation most type I IFN isoforms induced a characteristic and unique transcriptional pattern separate from other cytokines. These "signature" IFNs included; IFN-β, IFN-α2b/α2, IFN-αI, IFN-α2, IFN-αC, IFN-αJ1, IFN-αH2, and INF-α4B and induced the over-expression of 44 genes, all of which had known functional relationships with IFN such as myxovirus resistance (Mx)-1, Mx-2, and interferon-induced hepatitis C-associated microtubular aggregation protein. A second group of type I IFNs segregated separately and in closer association with the type II IFN-γ. The phylogenetic relationship of amino acid sequences among type I IFNs did not explain their sub-classification, although differences at positions 94 through 109 and 175 through 189 were present between the signature and other IFNs. Conclusion Seven IFN-α isoforms and IFN-β participate in the late phase polarization of MPs conditioned by LPS. This information broadens the previous view of the central role played by IFN-α in autoimmunity and tumor rejection by including and/or excluding an array of related factors likely to be heterogeneously expressed by distinct sub-populations of individuals in sickness or in response to biological therapy.</p

Gene expression profile of peripheral blood mononuclear cells in response to HIV-VLPs stimulation-1

0.005) in HIV-VLPs-treated PBMCs (A), MDDCs (B). The comparison between the two cell populations is shown in C. The clustering is defined by the dendrogram on the top of the clusterogram.<p><b>Copyright information:</b></p><p>Taken from "Gene expression profile of peripheral blood mononuclear cells in response to HIV-VLPs stimulation"</p><p>http://www.biomedcentral.com/1471-2105/9/S2/S5</p><p>BMC Bioinformatics 2008;9(Suppl 2):S5-S5.</p><p>Published online 26 Mar 2008</p><p>PMCID:PMC2323668.</p><p></p

Gene expression profile of peripheral blood mononuclear cells in response to HIV-VLPs stimulation-2

Hown. The gray boxes include the genes showing a differential expression >2 in both MDDCs and PBMCs induced with HIV-VLPs.<p><b>Copyright information:</b></p><p>Taken from "Gene expression profile of peripheral blood mononuclear cells in response to HIV-VLPs stimulation"</p><p>http://www.biomedcentral.com/1471-2105/9/S2/S5</p><p>BMC Bioinformatics 2008;9(Suppl 2):S5-S5.</p><p>Published online 26 Mar 2008</p><p>PMCID:PMC2323668.</p><p></p

Gene expression profile of peripheral blood mononuclear cells in response to HIV-VLPs stimulation-3

Ctively. The expression of CD80, CD83, CD86 and HLA-DR was analyzed on fixed cells by FACScalibur flow cytometer and data analysis was carried out with FlowJo software. The PBMCs were gated for the CD14 positivity. The results of a representative experiment are shown; the shadowed curve represents the untreated cells.<p><b>Copyright information:</b></p><p>Taken from "Gene expression profile of peripheral blood mononuclear cells in response to HIV-VLPs stimulation"</p><p>http://www.biomedcentral.com/1471-2105/9/S2/S5</p><p>BMC Bioinformatics 2008;9(Suppl 2):S5-S5.</p><p>Published online 26 Mar 2008</p><p>PMCID:PMC2323668.</p><p></p

Gene expression profile of peripheral blood mononuclear cells in response to HIV-VLPs stimulation-0

Ctively. The expression of CD80, CD83, CD86 and HLA-DR was analyzed on fixed cells by FACScalibur flow cytometer and data analysis was carried out with FlowJo software. The PBMCs were gated for the CD14 positivity. The results of a representative experiment are shown; the shadowed curve represents the untreated cells.<p><b>Copyright information:</b></p><p>Taken from "Gene expression profile of peripheral blood mononuclear cells in response to HIV-VLPs stimulation"</p><p>http://www.biomedcentral.com/1471-2105/9/S2/S5</p><p>BMC Bioinformatics 2008;9(Suppl 2):S5-S5.</p><p>Published online 26 Mar 2008</p><p>PMCID:PMC2323668.</p><p></p