The Lung Microenvironment Instructs Gene Transcription in Neonatal and Adult Alveolar Macrophages.

Immaturity of alveolar macrophages (AMs) around birth contributes to the susceptibility of newborns to lung disease. However, the molecular features differentiating neonatal and mature, adult AMs are poorly understood. In this study, we identify the unique transcriptomes and enhancer landscapes of neonatal and adult AMs in mice. Although the core AM signature was similar, murine adult AMs expressed higher levels of genes involved in lipid metabolism, whereas neonatal AMs expressed a largely proinflammatory gene profile. Open enhancer regions identified by an assay for transposase-accessible chromatin followed by high-throughput sequencing (ATAC-seq) contained motifs for nuclear receptors, MITF, and STAT in adult AMs and AP-1 and NF-κB in neonatal AMs. Intranasal LPS activated a similar innate immune response in both neonatal and adult mice, with higher basal expression of inflammatory genes in neonates. The lung microenvironment drove many of the distinguishing gene expression and open chromatin characteristics of neonatal and adult AMs. Neonatal mouse AMs retained high expression of some proinflammatory genes, suggesting that the differences in neonatal AMs result from both inherent cell properties and environmental influences.

Sialic Acid-Siglec-E Interactions Regulate the Response of Neonatal Macrophages to Group B Streptococcus.

The mammalian Siglec receptor sialoadhesin (Siglec1, CD169) confers innate immunity against the encapsulated pathogen group B Streptococcus (GBS). Newborn lung macrophages have lower expression levels of sialoadhesin at birth compared with the postnatal period, increasing their susceptibility to GBS infection. In this study, we investigate the mechanisms regulating sialoadhesin expression in the newborn mouse lung. In both neonatal and adult mice, GBS lung infection reduced Siglec1 expression, potentially delaying acquisition of immunity in neonates. Suppression of Siglec1 expression required interactions between sialic acid on the GBS capsule and the inhibitory host receptor Siglec-E. The Siglec1 gene contains multiple STAT binding motifs, which could regulate expression of sialoadhesin downstream of innate immune signals. Although GBS infection reduced STAT1 expression in the lungs of wild-type newborn mice, we observed increased numbers of STAT1+ cells in Siglece-/- lungs. To test if innate immune activation could increase sialoadhesin at birth, we first demonstrated that treatment of neonatal lung macrophages ex vivo with inflammatory activators increased sialoadhesin expression. However, overcoming the low sialoadhesin expression at birth using in vivo prenatal exposures or treatments with inflammatory stimuli were not successful. The suppression of sialoadhesin expression by GBS-Siglec-E engagement may therefore contribute to disease pathogenesis in newborns and represent a challenging but potentially appealing therapeutic opportunity to augment immunity at birth.

Ultrafast beam pattern modulation by superposition of chirped optical vortex pulses.

As an extension of pulse shaping techniques using the space-time coupling of ultrashort pulses or chirped pulses, we demonstrated the ultrafast beam pattern modulation by the superposition of chirped optical vortex pulses with orthogonal spatial modes. The stable and robust modulations with a modulation frequency of sub-THz were carried out by using the precise phase control technique of the constituent pulses in both the spatial and time/frequency domains. The performed modulations were ultrafast ring-shaped optical lattice modulation with 2, 4 and 6 petals, and beam pattern modulations in the radial direction. The simple linear fringe modulation was also demonstrated with chirped spatially Gaussian pulses. While the input pulse energy of the pulses to be modulated was 360 [Formula: see text]J, the output pulse energy of the modulated pulses was 115 [Formula: see text]J with the conversion efficiency of [Formula: see text] 32%. Demonstrating the superposition of orthogonal spatial modes in several ways, this ultrafast beam pattern modulation technique with high intensity can be applicable to the spatially coherent excitation of quasi-particles or collective excitation of charge and spin with dynamic degrees of freedom. Furthermore, we analyzed the Poynting vector and OAM of the composed chirped OV pulses. Although the ring-shaped optical lattice composed of OV pulse with topological charges of [Formula: see text] is rotated in a sub-THz frequency, the net orbital angular momentum (OAM) averaged over one optical period is found to be negligible. Hence, it is necessary to require careful attention to the application of the OAM transfer interaction with matter by employing such rotating ring-shaped optical lattices.