MicroRNA-146a reduces MHC-II expression via targeting JAK/STAT signaling in dendritic cells after stem cell transplantation.

Acute Graft-versus-host disease (GVHD) is a major immunological complication after allogeneic hematopoietic cell transplantation and a better understanding of the molecular regulation of the disease could help to develop novel targeted therapies. Here we found that a G/C polymorphism within the human microRNA-146a (miR-146a) gene of transplant recipients, which causes reduced miR-146a levels, was strongly associated with the risk of developing severe acute GVHD (n=289). In mice, deficiency of miR-146a in the hematopoietic system or transfer of recipient-type miR-146a-/- dendritic cells (DCs) enhanced GVHD, while miR-146a mimic-transfected DCs ameliorated disease. Mechanistically, lack of miR-146a enhanced JAK2-STAT1 pathway activity, which led to higher expression of class II-transactivator (CIITA) and consecutively increased MHCII-levels on DCs. Inhibition of JAK1/2 or CIITA knockdown in DCs prevented miR-146a-/- DC-induced GVHD exacerbation. Consistent with our findings in mice, patients with the miR-146a polymorphism rs2910164 in hematopoietic cells displayed higher MHCII levels on monocytes, which could be targeted by JAK1/2 inhibition. Our findings indicate that the miR-146a polymorphism rs2910164 identifies patients at high risk for GVHD before allo-HCT. Functionally we show that miR-146a acts as a central regulator of recipient-type DC activation during GVHD by dampening the pro-inflammatory JAK-STAT/CIITA/MHCII axis, which provides a scientific rationale for early JAK1/2 inhibition in selected patients.

[Ultrastructural characters defining the terms 'yeast cell', 'pseudomycelium' and 'true mycelium' in Candida albicans]. / Ultrastruktur-Merkmale zur Definition der Begriffe 'Hefezelle', 'Pseudomyzel' und 'echtes Myzel' bei Candida albicans.

The discrimination of the morphological elements, 'yeast cell', 'pseudomycelium' and 'true mycelium' is indispensable in the mycological and histopathological diagnostics of fungal infections caused by Candida albicans. However, precisely defined distinctive criteria are lacking in the medical mycological literature. Such criteria based upon electron microscopical studies of the cell wall, are described.

[The significance of Candida serology based on cell wall antigens]. / Zur Bewertung der Zellwandantigen-basierten Candida-Serologie.

The article reviews the state of the art in detecting anti-Candida antibodies directed against cell wall mannans. Experience in this field was collected over more than four decades. The mannan antigens of Candida spp. are well characterized serologically and biochemically. Candida mannans are immunogenically potent antigens to which the host's immune system reacts regularly. The human host is not immunologically naïve towards Candida albicans. Clinical and laboratory evaluation of methodologies detecting anti-Candida antibodies must essentially regard the pathogenetic particularities of candidaemia and candidosis with their opportunistic characters.

Antiapoptotic activity of bovine papilloma virus.

Transformed fibroblasts have been recently shown to be sensitive for induction of apoptosis by TGF-beta-treated neighbouring untransformed cells. Cells transformed by a variety of different transformation principles were regularly sensitive for intercellular induction of apoptosis, but fibroblasts transformed by bovine papillomavirus (BPV) represented a striking exception. In contrast to chemically transformed C127 cells, BPV-transformed C127 cells showed resistance against intercellular induction of apoptosis. In addition, BPV-transformed cells were resistant against induction of apoptosis by ROS in glutathione depleted cells. The antiapoptotic function of papillomaviruses may be of central importance for papillomavirus-induced tumor formation as it can protect transformed cells from intercellular control of oncogenesis.

Influence of amorolfine on the morphology of Candida albicans and Trichophyton mentagrophytes.

Amorolfine applied in concentrations of 0.1-100 micrograms/ml causes considerable damage to the ultrastructure of Candida albicans and Trichophyton mentagrophytes: electron-lucent areas appear in the cytoplasm; extracytoplasmic membrane vesicles are formed and deposited in the cell wall; starved fungal cells, with normal ultrastructure, can be found; lysed, dead cells demonstrate the process of severe ultrastructural damage; T. mentagrophytes cell walls especially increase in thickness. The extent of the damage caused by amorolfine is comparable to that produced by azole antifungals.

Influence of amorolfine on the morphology of Candida albicans and Trichophyton mentagrophytes.

Amorolfine applied in concentrations of 0.1-100 micrograms/ml causes considerable damage to the ultrastructure of Candida albicans and Trichophyton mentagrophytes: electron-lucent areas appear in the cytoplasm. Extracytoplasmic membrane vesicles are formed and deposited in the cell wall. Starved fungal cells, with normal ultrastructure, can be found. Lysed, dead cells demonstrate the process of severe ultrastructural damage. T. mentagrophytes cell walls especially increase in thickness. The feature of the damage caused by amorolfine is comparable to that produced by azole antifungals.

The effects of amorolfine and oxiconazole on the ultrastructure of Trichophyton mentagrophytes. A comparison.

Amorolfin applied in concentrations of 0.1-100 micrograms ml-1 caused considerable damages to the ultrastructure of Trichophyton mentagrophytes: Electron-transparent areas appear in the cytoplasma. The cell wall increases in thickness. Extracytoplasmic membrane vesicles are formed and deposited in the cell wall. Starved fungal cells, with normal ultrastructure, can be found. Lysed, dead cells demonstrate the process of final, vigorous ultrastructural damage. The feature of the damage caused by amorolfin is comparable to that effected by azole antifungals. The characteristics of the ultrastructural changes are similar to those due to amorolfin in the yeast species Candida albicans.