Neonatal development of mucosal immunity is a carefully regulated process that both influences and responds to progressive microbial exposure in the infant intestines. Hand, Hornef and colleagues review how the phases of mucosal development provide important and non-redundant functions toward establishing immediate and long-term immune homeostasis.

Investigators have long suspected a link between inflammation and depression, but the underlying mechanisms are not well understood. Fang et al. report that lipopolysaccharide-binding protein regulates monoamine biosynthesis and might be a missing link and potential therapeutic target for inflammation-associated depressive behaviors.

STING transverses the endoplasmic reticulum (ER), Golgi, and endosomal compartments before its degradation within the lysosomes. In this issue of Immunity, Fang et al. demonstrate that the enrichment of cholesterol and sphingomyelin in the trans-Golgi network and endosomes mediated by the ARMH3-PI4KB-PI4P pathway plays a pivotal role in STING activation under cGAS-dependent and -independent…

Respiratory infection can trigger exacerbation of emphysema, but we lack understanding of the processes involved. Wang et al. show that alteration of a COPD variant gene in the stroma can potentiate tissue-resident lymphocyte expansion that suppresses stem cell renewal, leading to loss of barrier surface and emphysema in the lung.

The early cellular targets of HIV and the mechanisms of viral dissemination in humans remain elusive. Gantner et al. demonstrate that the early targets of HIV rapidly change during acute infection and differ between blood and lymph nodes. They also observe that latent and genetically intact proviruses persisting during therapy are archived from the earliest stages of acute infection.

Pan-betacoronavirus broadly neutralizing antibodies (bnAbs) may hold the key to developing broadly protective vaccines against pandemic coronaviruses and SARS-CoV-2 variants. Zhou et al. isolate a large panel of S2 stem-helix bnAbs to betacoronaviruses and reveal their public features. Select stem-helix bnAbs protect against all three human betacoronaviruses that cause deadly disease.