Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria

Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/β-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-α/β immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-γ are, both quantitatively and qualitatively, much stronger than those to IFN-α/β. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-γ. By contrast, IFN-α/β-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-γ-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-α/β-dependent antiviral immunity

Audit Firm Tenure and Audit Quality Implied by Discretionary Accruals and Modified Opinions: Evidence from Turkey

Accounting scandals and bankruptcies across the world have raised concerns about the financial statement audit quality. Though, prior results documented mixed results, some argue that auditors become more familiar with the client and therefore independence is impaired when audit firm tenure gets longer. Consequently, some regulators set a limit on the number of years an audit firm may audit the same client. This study examines the association between audit firm tenure and audit quality in Turkey. We used three measures to proxy audit quality such as propensity to issue modified audit reports and discretionary accruals determined by two models. We found some evidence that audit quality does not increase with limited audit firm tenure. Given the additional costs associated with audit switch, it is concluded that there are minimal benefits of mandatory firm rotation. The results of this study will be useful for the regulators who are in charge to improve the audit quality