LXR signaling controls homeostatic dendritic cell maturation

Dendritic cells (DCs) mature in an immunogenic or tolerogenic manner depending on the context in which an antigen is perceived, preserving the balance between immunity and tolerance. Whereas the pathways driving immunogenic maturation in response to infectious insults are well-characterized, the signals that drive tolerogenic maturation during homeostasis are still poorly understood. We found that the engulfment of apoptotic cells triggered homeostatic maturation of conventional cDC1s within the spleen. This maturation process could be mimicked by engulfment of empty, non-adjuvanted lipid nanoparticles (LNPs), was marked by intracellular accumulation of cholesterol, and highly unique to type 1 DCs. Engulfment of either apoptotic cells or cholesterol-rich LNPs led to activation of the LXR pathway, which promotes the efflux of cellular cholesterol, and repressed genes associated with immunogenic maturation. In contrast, simultaneous engagement of TLR3 to mimic viral infection via administration of poly(I:C)-adjuvanted LNPs repressed the LXR pathway, thus delaying cellular cholesterol efflux and inducing genes that promote T cell-mediated immunity. These data demonstrate that conserved cellular cholesterol efflux pathways are differentially regulated in in tolerogenic versus immunogenic cDC1s and suggest that administration of non-adjuvanted cholesterol-rich LNPs may be an approach for inducing tolerogenic DC maturation

Arrival date and territorial behavior are associated with corticosterone metabolite levels in a migratory bird

International audienceGlucocorticoids promote the mobilization of energy stores and they may facilitate the expression of energetically expensive functions. Early arrival on the breeding grounds in migratory species and territorial competition are energetically demanding activities that may be supported by elevated baseline glucocorticoid levels. Here, we evaluated the associations between the baseline levels of excreted corticosterone (CORT) metabolites of male Pied Flycatchers () just after arriving on their breeding area and timing of arrival, considering ornamental traits indicative of social status, like forehead patch size and black plumage coloration, as well as heat shock protein levels (HSP60). We observed a positive association of CORT metabolites with HSP60 levels, which are synthesized under several environmental challenges affecting cell homeostasis. Our data showed a negative association between arrival date and CORT metabolite levels, possibly as a result of the higher energetic demands imposed by the hard environmental conditions experienced at the time of an early arrival after migration. We observed a negative relationship of forehead patch dimensions and CORT metabolite levels, suggesting that dominance is associated with low baseline CORT metabolites. Also, males that expressed a higher degree of territorial behaviour when exposed to a playback song of a conspecific at their nest-box showed higher CORT metabolites upon arrival than males that expressed a lower degree of territorial behavior. This may indicate that elevated baseline CORT metabolite levels may facilitate an intense territorial competition in males. Thus, male–male competition may be a factor affecting observed baseline glucocorticoid levels in migratory birds