Antiviral immune responses play as a double edged sword in resolution of infection and pathogenesis of acute lung injury caused by infection with highly pathogenic influenza A viruses. Here we show that type I interferons (IFNs) are important in protection against acute influenza A virus infection not only via their antiviral activity but also via their anti-inflammatory activity. IFN α receptor (IFNAR) knock-out (KO) mice exhibited increased mortality and morbidity with higher viral load after infection with influenza virus A/FM/1/47 (H1N1, a mouse-adapted strain) compared with wild-type (WT) mice, though the viruses were finally eliminated in both groups. The levels of proinflammatory cytokines in the lungs were significantly higher, while the level of IL-10 in the lungs was significantly lower in IFNAR KO mice than in WT mice during the course of infection. Restoration of IL-10 during an ongoing virus infection significantly reduced the levels of proinflammatory cytokines and improved mortality of IFNAR KO mice. These results suggest that type I IFNs are responsible not only for direct resolution of viral load but also for suppression of immunopathology caused by influenza A virus through IL-10 production.

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Type I interferons (IFNs) promote natural killer (NK) and CD8⁺ T-cell responses, which play a role not only in the resolution of infection but also in the induction of acute lung injury following influenza A virus infection. We show here that IFN-α receptor knock-out (Ifnar1^-/-) mice exhibited impaired cytotoxic activity as well as an increased ability of NK and CD8⁺ T cells to produce IFN-γ after infection with influenza virus A/FM/1/47 (H1N1, a mouse-adapted strain). A deficiency in IFNAR signaling significantly impaired IL-10 production in influenza virus-infected lungs and enhanced IFN-γ production by NK cells, which were suppressed by exogenous IL-10. Depletion of NK cells but not CD8⁺ T cells in Ifnar1^-/- mice improved the survival rate after A/FM/1/47 infection, indicating that NK cells are responsible for acute lung injury in Ifnar1^-/- mice following influenza A virus infection, although the depletion of IFN-γ did not improve the outcome. Thus, type I IFN signaling plays a role not only in the upregulation of cytotoxicity but also in the downregulation of some effector mechanisms including IFN-γ production by NK and CD8⁺ T cells via IL-10 production.

A 39-year-old man treated with dasatinib for chronic myelogenous leukaemia presented to our hospital with haemoptysis, coughing, and dyspnoea. Chest radiography and computed tomography revealed ground-glass opacities and a crazy-paving pattern. Bronchoalveolar lavage was not performed due to serious hypoxemia and bleeding. Significant bleeding from the peripheral bronchi led to a diagnosis of an alveolar haemorrhage. Dasatinib-induced alveolar haemorrhaging was suspected based on the clinical findings. His condition improved immediately after dasatinib withdrawal and initiation of steroid therapy. Reports of alveolar haemorrhaging induced by dasatinib are rare. As such, this is considered an important case.

We describe sibling cases presenting with long-standing, slowly progressive proximal muscle weakness without joint contractures or hyperlaxity. Whole-exome sequence analysis showed compound heterozygous mutations including a novel stop codon mutation of p.*1020Yext*86 (c.3060G > C) in COL6A2 as the causative mutations, establishing the diagnosis of COL6A2-related myopathy presenting with limb girdle muscular dystrophy phenotype with autosomal recessive inheritance. Collagen VI-related myopathies should be considered in patients with early childhood-onset, slowly progressive proximal weakness even without joint contractures.