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Tuberculosis (TB) induced by Mycobacterium tuberculosis (M. tuberculosis) infection remains a global most deadly infectious disease. While development of more effective TB vaccines and therapeutics relies on identifications of true biomarkers designating an immune protection against M. tuberculosis infection, exact protective immune components against M. tuberculosis infection remain largely unidentified. We previously found that severe TB induced remarkable up-regulation of interferon regulatory factor 7 (IRF7) and IRF7-related gene signatures, implicating that some unknown downstream molecules in IRF7 signaling cascades may determine the M. tuberculosis infection outcomes and serve as a protective immune component against M. tuberculosis infection. Indeed, here, we observe that genetic ablation of IRF7 leads to more severe lung pathology, increased M. tuberculosis burdens, impaired differentiation of effector/memory T subsets, and extensively elevated expression of pro-inflammatory cytokines in lungs. Importantly, IRF7 is vital for sustaining expression of PD-1/PD-L1 and PD-1/PD-L1-modulated miRNA-31. Moreover, interventions of miRNA-31 expressions via administration of miRNA-31 agomir reduces lung pathology and bacilli burdens via inducing up-regulation of gene sets involved in biological processes of defense response or cellular and chemical homeostasis in lungs. Thus, this study uncovers previously unrecognized importance and mechanisms of IRF7-mediated miRNA-31 as a protective immune component against M. tuberculosis infection. [ABSTRACT FROM AUTHOR]

Summary: IL-22 has been suggested to play an important role in immune response against Mycobacterium tuberculosis infection. However, the exact role of IL-22 in human tuberculosis (TB) infection remains unclear and the regulatory mechanism of IL-22 response in human TB is unknown. In this study, we observed that successful anti-tuberculosis treatment induced an enhanced and sustained M. tuberculosis antigen-specific IL-22 response, correlated with the decrease of the frequencies of CD19+CD5+CD1d+ regulatory B cells. We also found that depletion of CD19+ B cells significantly enhanced M. tuberculosis antigen-specific IL-22 production by peripheral blood mononuclear cells. More importantly, we observed that purified CD19+ B cells, and more efficiently, CD19+CD5+CD1d+ regulatory B cells, suppressed IL-22 production. In summary, we showed here for the first time that effective anti-tuberculosis treatment restores M. tuberculosis antigen-specific IL-22 response through a novel mechanism by reducing the frequencies of CD19+CD5+CD1d+ regulatory B cells in human TB. [Copyright &y& Elsevier]

Abstract: The surface morphology of GaInP buffer layers mismatched to GaAs substrate is probed to study its impact on the distribution of self-organized InP island. The steps, facet island matrix and mismatch dislocations formed sequentially as Ga content increased in buffer layers. And the lateral distribution of InP island can be controlled efficiently by the steps, island matrix and mismatch dislocation. The island matrix, with about 100nm periodicity, is found to be efficient to obtain InP island lateral distribution with 1μm periodicity on sample 3. The result also shows the dislocation had different functions to control the island distribution along different directions, [110] and directions. [Copyright &y& Elsevier]

CD4+/CD8+ T cells play a major role in conferring immune protection against tuberculosis (TB), but it remains unknown how the immune responses of CD4+/CD8+ T cells exactly correlate with the clinical variables and disease statuses during anti-TB chemotherapy. To address this, several major immune parameters of CD4+/CD8+ T cells in peripheral blood derived from pulmonary TB patients and healthy volunteers were evaluated. We observed that active TB infection induced lower CD3+ T cell and CD4+ T cell levels but higher CD8+T cell levels, while anti-TB chemotherapy reversed these effects. Also, anti-TB treatment induced enhanced production of IL-2 and IFN-γ but reduced expression of IL-10 and IL-6. Moreover, the dynamic changes of CD3, CD4, and CD8 levels did not show a significant association with sputum smear positivity. However, the frequencies of IL-2+CD4+ or IL-10 + CD4+ T effector subpopulation or IL-1β production in peripheral blood showed significant difference between patients positive for sputum smear and patients negative for sputum smear after anti-TB treatment. These findings implicated that recovery of Th1/CD8+T cell effector levels might be critical immunological events in pulmonary TB patients after treatment and further suggested the importance of these immunological parameters as potential biomarkers for prediction of TB progress and prognosis. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we mainly investigated the expression of IFN-γ and IL-22-producing CD4+T cells, the relationship between the two cytokines in human tuberculosis. We showed that IFN-γ and IL-22 were induced by human mycobacterial infection. Besides, CD4+T cells expressing IFN-γ and IL-22 were significantly elevated following PPD stimulation. In addition, IFN-γ and IL-22 -expressing CD4+T cells were distinct from each other. We also found that there was a reciprocal relationship between IFN-γ and IL-22 production. The production of IL-22 was markedly enhanced in the absence of IFN-γ, also, the expression of IFN-γ was increased when the IL-22 signaling was inhibited by monoclonal anti-IL-22 mAb. Furthermore, data revealed that the detectable IL-22 affected the phynotype of IFN-γ+CD4+T cells. IL-22 induced up-regulation of CD27 expression in IFN-γ+CD4+T cells, which might further confirm that IL-22 had an effect on the response of IFN-γ. Thus, this work provides a previous unknown relationship between IFN-γ and IL-22 in human TB disease. [Copyright &y& Elsevier]