Human dendritic cell subsets display distinct interactions with the pathogenic mould Aspergillus fumigatus.

The mould Aspergillus fumigatus is primarily an opportunistic pathogen of immunocompromised patients. Once fungal spores have been inhaled they encounter cells of the innate immune system, which include dendritic cells (DCs). DCs are the key antigen-presenting cells of the immune system and distinct subtypes, which differ in terms of origin, morphology and function. This study has systematically compared the interactions between A. fumigatus and myeloid DCs (mDCs), plasmacytoid DCs (pDCs) and monocyte-derived DCs (moDCs). Analyses were performed by time-lapse video microscopy, scanning electron microscopy, plating assays, flow cytometry, 25-plex ELISA and transwell assays. The three subsets of DCs displayed distinct responses to the fungus with mDCs and moDCs showing the greatest similarities. mDCs and moDCs both produced rough convolutions and occasionally phagocytic cups upon exposure to A. fumigatus whereas pDCs maintained a smooth appearance. Both mDCs and moDCs phagocytosed conidia and germ tubes, while pDCs did not phagocytose any fungi. Analysis of cytokine release and maturation markers revealed specific differences in pro- and anti-inflammatory patterns between the different DC subsets. These distinct characteristics between the DC subsets highlight their differences and suggest specific roles of moDCs, mDCs and pDCs during their interaction with A. fumigatus in vivo.

Aspergillus fumigatus induces microRNA-132 in human monocytes and dendritic cells.

Aspergillus fumigatus is responsible for severe and often fatal infections in immunocompromised patients. The human immune response against this pathogenic mould is still not fully understood. Recently, microRNAs (miRNAs) have been characterized as regulators of inflammation and immune response in various diseases. MiRNAs specifically bind to mRNA target sequences, thereby leading to gene silencing by target degradation and/or translational repression. To investigate the possible role of miRNAs during A. fumigatus infection, we studied the expression of two major immune relevant miRNAs, miR-132 and miR-155, in human monocytes and dendritic cells (DCs). Both cell types are crucial for the immune response against A. fumigatus. Here, we demonstrate for the first time that miR-132 and miR-155 are differentially expressed in monocytes and DCs upon stimulation with A. fumigatus or bacterial lipopolysaccharide (LPS). Interestingly, miR-132 was induced by A. fumigatus but not by LPS in both cell types. Our data suggest that miR-132 may be a relevant regulator of the immune response directed against A. fumigatus.