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Recognition of pathogen-associated molecular patterns can trigger the inositol-requiring enzyme 1 α (IRE1α) arm of the endoplasmic reticulum (ER) stress response in innate immune cells. This process maintains ER homeostasis and also coordinates diverse immunomodulatory programs during bacterial and viral infections. However, the role of innate IRE1α signaling in response to fungal pathogens remains elusive. Here, we report that systemic infection with the human opportunistic fungal pathogen Candida albicans induced proinflammatory IRE1α hyperactivation in myeloid cells that led to fatal kidney immunopathology. Mechanistically, simultaneous activation of the TLR/IL-1R adaptor protein MyD88 and the C-type lectin receptor dectin-1 by C. albicans induced NADPH oxidase–driven generation of ROS, which caused ER stress and IRE1α-dependent overexpression of key inflammatory mediators such as IL-1β, IL-6, chemokine (C-C motif) ligand 5 (CCL5), prostaglandin E2 (PGE2), and TNF-α. Selective ablation of IRE1α in leukocytes, or treatment with an IRE1α pharmacological inhibitor, mitigated kidney inflammation and prolonged the survival of mice with systemic C. albicans infection. Therefore, controlling IRE1α hyperactivation may be useful for impeding the immunopathogenic progression of disseminated candidiasis.

Although the graphitic carbon contamination of synchrotron beamline optics has been an obvious problem for several decades, the basic mechanisms underlying the contamination process as well as the cleaning/remediation strategies are not understood and the corresponding cleaning procedures are still under development. In this study an analysis of remediation strategies all based on in situ low-pressure RF plasma cleaning approaches is reported, including a quantitative determination of the optimum process parameters and their influence on the chemistry as well as the morphology of optical test surfaces. It appears that optimum results are obtained for a specific pressure range as well as for specific combinations of the plasma feedstock gases, the latter depending on the chemical aspects of the optical surfaces to be cleaned.