Age-associated impaired plasmacytoid dendritic cell functions lead to decreased CD4 and CD8 T cell immunity

Increased susceptibility to infections, particularly respiratory viral infections, is a hallmark of advancing age. The underlying mechanisms are not well understood, and there is a scarcity of information regarding the contribution of the innate immune system, which is the first line of defense against infections. In the present study, we have investigated the effect of advancing age on plasmacytoid dendritic cell (PDC) function because they are critical in generating a robust antiviral response via the secretion of interferons (IFN). Our results indicate that PDCs from the aged are impaired in their capacity to secrete IFN-I in response to influenza virus and CPG stimulation. Additionally, we observed a severe reduction in the production of IFN-III, which plays an important role in defense against viral infections at respiratory mucosal surfaces. This reduction in IFN-I and IFN-III were a result of age-associated impaired phosphorylation of transcription factor, IRF-7. Furthermore, aged PDCs were observed to be impaired in their capacity to induce perforin and granzyme in CD8 T cells. Comparison of the antigen-presenting capacity of aged PDC with young PDC revealed that PDCs from aged subjects display reduced capacity to induce proliferation and IFN-gamma secretion in CD4 and CD8 T cells as compared with PDCs from young subjects. In summary, our study demonstrates that advancing age has a profound effect on PDC function at multiple levels and may therefore, be responsible for the increased susceptibility to infections in the elderly

The intergroup sensitivity effect in mergers and acquisitions: Testing the role of merger motives

Research has shown that people are more defensive to criticism when it stems from an outgroup member, compared to an ingroup member (the intergroup sensitivity effect: ISE). We conducted two online vignette experiments to examine the ISE in the context of an organizational merger and the role of merger motives for the ISE. We predicted that the ISE would also emerge in mergers and acquisitions (M&As), but people would respond less negatively to criticism from the outgroup when the motive for the merger is described as achieving synergies rather than growth. In Experiment 1 (N = 452), which did not mention any motives behind the acquisition, a significant ISE emerged. Experiment 2 (N = 587) again showed an ISE regardless of the merger motive. In both experiments, the ISE was mediated by perceptions of the outgroup criticism as less legitimate and constructive. Overall, this research points to the intergroup sensitivity effect as a relevant phenomenon during post-merger integration