Corrigendum: Monocyte signature as a predictor of chronic lung disease in the preterm infant.

[This corrects the article DOI: 10.3389/fimmu.2023.1112608.].

Monocyte signature as a predictor of chronic lung disease in the preterm infant.

Introduction: Inflammation is a key driver of morbidity in the vulnerable preterm infant exposed to pre- and postnatal hazards and significantly contributes to chronic lung disease, i.e. bronchopulmonary dysplasia (BPD). However, the early changes in innate immunity associated with BPD development are incompletely understood. Methods: In very immature preterm infants below 32 weeks gestational age (GA; n=30 infants), monocyte subtypes were identified by Flow Cytometry at birth and throughout the postnatal course including intracellular TNF expression upon LPS stimulation. Complementing these measurements, cytokine end growth factor expression profiles (Luminex® xMAP®; n=110 infants) as well as gene expression profiles (CodeLinkTM Human I Bioarray; n=22) were characterized at birth. Results: The abundance of monocyte subtypes differed between preterm and term neonates at birth. Specifically, CD14++CD16+ (intermediate) monocytes demonstrated a dependency on PMA and elevated levels of nonclassical (CD14+CD16++) monocytes characterized preterm infants with developing BPD. Postnatally, lung injury was associated with an increase in intermediate monocytes, while high levels of nonclassical monocytes persisted. Both subtypes were revealed as the main source of intracellular TNF-α expression in the preterm infant. We identified a cytokine and growth factor expression profile in cord blood specimen of preterm infants with developing BPD that corresponded to the disease-dependent regulation of monocyte abundances. Multivariate modeling of protein profiles revealed FGF2, sIL-2 Rα, MCP-1, MIP1a, and TNF-α as predictors of BPD when considering GA. Transcriptome analysis demonstrated genes predicting BPD to be overrepresented in inflammatory pathways with increased disease severity characterized by the regulation of immune and defense response pathways and upstream regulator analysis confirmed TNF-α, interleukin (IL) -6, and interferon α as the highest activated cytokines in more severe disease. Whereas all BPD cases showed downstream activation of chemotaxis and activation of inflammatory response pathways, more severe cases were characterized by an additional activation of reactive oxygen species (ROS) synthesis. Discussion: In the present study, we identified the early postnatal presence of nonclassical (CD14+CD16++) and intermediate (CD14++CD16+) monocytes as a critical characteristic of BPD development including a specific response pattern of monocyte subtypes to lung injury. Pathophysiological insight was provided by the protein and transcriptome signature identified at birth, centered around monocyte and corresponding granulocyte activation and highlighting TNFα as a critical regulator in infants with developing BPD. The disease severity-dependent expression patterns could inform future diagnostic and treatment strategies targeting the monocytic cell and its progeny.

Shades of gray mouse lemurs: Ontogeny of female dominance and dominance-related behaviors in a nocturnal primate.

The ontogeny and establishment of dominance relationships in young individuals have been investigated in various group-living, diurnal primates but respective information is almost entirely lacking for nocturnal, non-gregarious species. As in many other mammals male primates often represent the dominant sex, but the opposite phenomenon (female dominance) is particularly frequent in lemurs, although almost nothing is known about its development. Therefore, we investigated the development of intersexual dominance in parallel to age-related changes in other relevant behaviors in the gray mouse lemur, a solitary forager with female dominance. In particular, the temporal trajectories of social play, marking behavior, social tolerance, and agonistic behaviors were characterized in captive dyads of three different age categories (ACs), among juveniles (ACI: 4-5 months, N = 6), adolescents (ACII: 8-9 months, N = 8) and young adults (ACIII: 12-13 months, N = 8). Data were collected during a series of three encounter experiments between one male and one female per dyad and age category (total observation time: 49.5 hr). Play behavior was observed in all age classes, although the number of playing dyads decreased with increasing age. A significant age-dependent increase in marking behavior was found in females, especially in substrate rubbing and urine washing, but not in males. Although conflict rates did not differ significantly between ACs, females started to win more conflicts from ACII onwards, and social tolerance decreased partly with increasing age. Clear dominance relationships were not observed in ACI and first indications of dominant females were found in ACII with an increasing number in ACIII. This study provides first information about the ontogeny of female dominance in a nocturnal primate and shows that this behavior develops relatively late during ontogeny. In conclusion, this study provides evidence for significant changes in the social lives of maturing mouse lemurs and a rather late social maturation in this species.