As sessile organisms, plants have evolved multiple mechanisms to respond to environmental changes to improve survival. Arabidopsis plants show accelerated flowering at increased temperatures. Here we show that Jumonji-C domain-containing protein JMJ30 directly binds to the flowering-repressor FLOWERING LOCUS C (FLC) locus and removes the repressive histone modification H3 lysine 27 trimethylation (H3K27me3). At elevated temperatures, the JMJ30 RNA and protein are stabilized, and FLC expression is maintained at high levels to prevent extreme precocious flowering. The double mutant of JMJ30 and its homologue JMJ32, grown at elevated temperatures, exhibits an early-flowering phenotype similar to the flc mutant, which is associated with increased H3K27me3 levels at the FLC locus and decreased FLC expression. Furthermore, ectopic expression of JMJ30 causes an FLC-dependent lateflowering phenotype. Taken together, JMJ30/JMJ32-mediated histone demethylation at the FLC locus constitutes a balancing mechanism in flowering control at warm temperatures to prevent premature early flowering.

Vitamin D level is linked to susceptibility to infections, but its relevance in candidemia is unknown. We aimed to investigate the in vivo sequelae of vitamin D3 supplementation in systemic Candida infection. Implicating the role of vitamin D in Candida infections, we showed that candidemic patients had significantly lower 25-OHD concentrations. Candida-infected mice treated with low-dose 1,25(OH)2D3 had reduced fungal burden and better survival relative to untreated mice. Conversely, higher 1,25(OH)2D3 doses led to poor outcomes. Mechanistically, low-dose 1,25(OH)2D3 induced proinflammatory immune responses. This was mediated through suppression of SOCS3 and induction of vitamin D receptor binding with the vitamin D-response elements in the promoter of the gene encoding interferon γ. These beneficial effects were negated with higher vitamin D3 doses. While the antiinflammatory effects of vitamin D3 are well described, we found that, conversely, lower doses conferred proinflammatory benefits in Candida infection. Our study highlights caution against extreme deviations of vitamin D levels during infections.

Invasive aspergillosis (IA) is a major opportunistic fungal infection in patients with haematological malignancies. Morbidity and mortality rates are high despite anti-fungal treatment, as the compromised status of immune system prevents the host from responding optimally to conventional therapy. This raises the consideration for immunotherapy as an adjunctive treatment. In this study, we evaluated the utility of expanded human NK cells as treatment against Aspergillus fumigatus infection in vitro and in vivo. The NK cells were expanded and activated by K562 cells genetically modified to express 4-1BB ligand and membrane-bound interleukin-15 (K562-41BBL-mbIL-15) as feeders. The efficacy of these cells was investigated in A. fumigatus killing assays in vitro and as adoptive cellular therapy in vivo. The expanded NK cells possessed potent killing activity at low effector-to-target ratio of 2:1. Fungicidal activity was morphotypal-dependent and most efficacious against A. fumigatus conidia. Fungicidal activity was mediated by dectin-1 receptors on the expanded NK cells leading to augmented release of perforin, resulting in enhanced direct cytolysis. In an immunocompromised mice pulmonary aspergillosis model, we showed that NK cell treatment significantly reduced fungal burden, hence demonstrating the translational potential of expanded NK cells as adjunctive therapy against IA in immunocompromised patients.