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Pathogenesis of Tuberculosis
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Divya B. Reddy, Jerrold J. Ellner
Immunosuppression makes the diagnosis of TB in persons living with HIV challenging. Several biosignatures that can accurately detect active TB from other lung diseases in HIV-infected individuals have now been identified.269–273 Differential gene expression of activating Fcγ receptor (FcGR1A) is of particular interest as it has been shown to successfully distinguish active TB from latent TB regardless of HIV status or genetic background.274 Gene expression of BATF2 has also been shown to have a high-negative predictive value in diagnosing active TB-coinfected individuals.275 In fact, recently Verma et al. have shown that gene expression of FcGR1A and BATF2 in addition to plasma protein levels of IFN-γ and CXCL10 have the potential to identify active TB even in advanced HIV patients with a CD4 count of <100 cells/μL).276
IL-6 augments IL-4-induced polarization of primary human macrophages through synergy of STAT3, STAT6 and BATF transcription factors
Published in OncoImmunology, 2018
Sahil Gupta, Arpit Jain, Shahzad Nawaz Syed, Ryan G. Snodgrass, Beatrice Pflüger-Müller, Matthias S. Leisegang, Andreas Weigert, Ralf P. Brandes, Ingo Ebersberger, Bernhard Brüne, Dmitry Namgaladze
We validated transcriptome changes revealed by RNA sequencing for selected synergistically induced genes with known functions in macrophages by Q-PCR and protein expression analyses. Particularly, dual stimulation enhances the expression of several chemokines targeted by IL-4 (CCL17, CCL18, CCL23 and CCL8). We observed induction of TGFA gene encoding an EGF receptor ligand as well as upregulation of CD274, coding for an immunosuppressive PD-L1 cell surface receptor at mRNA (Figure 2A) and protein levels (Figure 2B, C). We also validated genes uniquely induced by dual stimulation (Suppl. Figure 2A), including membrane receptors (CFI, CLEC7A) and chemokines (CCL2, CXCL13). In addition, we confirmed that IL-4 stimulation antagonized some IL-6 target genes (e.g. CD163 and FCGR1A) (Suppl. Figure 2B, 2C). Since the inhibitory immunoglobulin receptor FCGR2B was synergistically upregulated after IL-4/IL-6 co-treatment (Suppl. Table S4), we measured the expression levels of IgG Fc receptors and found upregulation of the inhibitory receptor FCGR2B at mRNA and protein level, whereas the activation receptors, FCGR1A and FCGR3A were downregulated in IL-4- and IL-4/IL-6-treated cells (Suppl. Figure 2 C-E). Analysis of typical markers associated with anti-inflammatory macrophage polarization revealed that CD206 mRNA expression was enhanced in dual stimulation as compared to control and single cytokine stimulations, but there were no alterations of IL-10 and TGFB1 mRNA expression relative to control or individual treatments (Suppl. Figure 2F).