OTULIN haploinsufficiency predisposes to environmentally directed inflammation.

Recently, OTULIN haploinsufficiency was linked to enhanced susceptibility to Staphylococcus aureus infections accompanied by local necrosis and systemic inflammation. The pathogenesis observed in haploinsufficient patients differs from the hyperinflammation seen in classical OTULIN-related autoinflammatory syndrome (ORAS) patients and is characterized by increased susceptibility of dermal fibroblasts to S. aureus alpha toxin-inflicted cytotoxic damage. Immunological abnormalities were not observed in OTULIN haploinsufficient patients, suggesting a non-hematopoietic basis. In this research report, we investigated an Otulin+/- mouse model after in vivo provocation with lipopolysaccharide (LPS) to explore the potential role of hematopoietic-driven inflammation in OTULIN haploinsufficiency. We observed a hyperinflammatory signature in LPS-provoked Otulin+/- mice, which was driven by CD64+ monocytes and macrophages. Bone marrow-derived macrophages (BMDMs) of Otulin+/- mice demonstrated higher proinflammatory cytokine secretion after in vitro stimulation with LPS or polyinosinic:polycytidylic acid (Poly(I:C)). Our experiments in full and mixed bone marrow chimeric mice suggest that, in contrast to humans, the observed inflammation was mainly driven by the hematopoietic compartment with cell-extrinsic effects likely contributing to inflammatory outcomes. Using an OTULIN haploinsufficient mouse model, we validated the role of OTULIN in the regulation of environmentally directed inflammation.

Close-range cues used by males of Polistes dominula in sex discrimination.

Sexual pheromones are chemical molecules responsible for mediating sex recognition and mating events. Long- and close-range sexual pheromones act differently. The first type is released to attract potential partners, whereas the second coordinates the interactions after potential mating partners encounter each other. Cuticular hydrocarbons (CHCs) have been suggested to be important cues in the mating systems of several Hymenoptera species, although empirical data are still lacking for many species. Here, we evaluated whether males of the model species Polistes dominula can differentiate the sex of individuals based on their CHC composition. In August 2019, several post-worker emergent nests (n = 19) were collected in the vicinity of Leuven (Belgium) and taken to the lab (KU Leuven), where newly emerged females and males were sampled, marked individually, and kept in plastic boxes for at least a week before being used in the mating trials. Focal males were paired with females and males from different nests and subjected to five different conditions: (I) alive, (II) dead, (III) CHCs washed, (IV) CHCs partially returned, and (V) CHCs from the opposite sex. We videotaped the interactions for 10 min and analysed the duration and different behavioural interactions of the focal male. Our results indicate that CHCs may be used by males as cues to recognise a potential mating partner in P. dominula, since the focal males displayed specific courtship behaviours exclusively toward females. Although we cannot exclude that visual cues could also be used in combination with the chemical ones, we empirically demonstrate that CHCs may be important to convey sexual information at close range in mating systems, allowing fast decisions toward potential sexual partners or rivals.