Letters

Robbiani and colleagues show that antibodies against specific chemokines are detected in COVID-19 convalescents and may modulate the inflammatory response and disease outcome.

Aifantis and colleagues use leukemic cell lines to identify modulators of CD19 expression that have the potential to improve therapeutic strategies.

Maini and colleagues used bronchoalveolar lavage (BAL) samples from the lower respiratory tract of healthy donors obtained before the COVID-19 pandemic to show airway-resident cross-reactive T cells are present in pre-pandemic BAL, and correlated with the strength of human coronavirus immunity

Serafini and colleagues show that intestinal villus ILC3s, which are largely immotile at steady state, develop a patrolling behavior in response to inflammation.

Delaying a second COVID-19 vaccine dose is a common strategy to maximize vaccine coverage, but the immunological effects are unclear. Hall et al. demonstrate that a delayed second dose significantly enhances neutralizing humoral immunity.

Phetsouphanh and colleagues show that individuals with long COVID have persistent activation of the innate and adaptive immune system at 8 months after infection and define a set of analytes associated with long COVID.

The immunological processes occurring in the upper respiratory tract during COVID-19 are relatively poorly understood. Jochems and colleagues observe durable changes in the upper respiratory tract following SARS-CoV-2 infection, including evidence of virus-specific tissue memory T cells.

Lanz and colleagues show that the first dose of the BNT162b2 mRNA vaccine against SARS-CoV-2 activates a non-neutralizing recall response predominantly targeting the S2 subunit of the spike protein, while the second dose boosts neutralizing antibodies specific for the receptor binding domain of the spike protein.

ILC2 metabolism has been largely unexplored. Di Santo and colleagues examine metabolic profiles from naive and cytokine-activated ILC2s and find that IL-33-triggered ILC2s rely on distinct metabolic pathways to sustain proliferation and function.

Scheiermann and colleagues show that circadian clocks control the infiltration of dendritic cells into skin lymphatics in mice and humans, with a peak migration to the lymph nodes during the rest phase.

RIG-I is a cytosolic nucleic acid sensor triggering type I IFN production. Takaoka and colleagues find that RIG-I recognizes SARS-CoV-2 RNA in a noncanonical manner and fails to activate type I IFN, but it directly restricts viral replication.

Andreakos and colleagues provide a longitudinal study comparing patients with COVID-19 to patients infected with influenza. They report a dysregulated interferon response whereby IFN-λ and type I IFN production were diminished and delayed in patients with COVID-19, exhibiting a response that is ‘untuned’ with other inflammatory cytokines.

Mantovani and colleagues report elevated circulating concentrations of the long pentraxin PTX3 in patients with severe COVID-19. Within this cohort, early detection of high PTX3 concentrations emerged as a strong predictor of decreased survival.

Farber and colleagues report distinct antibody responses to SARS-CoV-2 in pediatric cohorts, including those who developed multisystem inflammatory syndrome (MIS-C), and adult COVID-19 cohorts.

Huppa and colleagues highlight signaling deficiencies in chimeric antigen receptor (CAR)-modified T cells that limit the efficacy of CAR T cell therapies to target tumors with diminished antigen expression.

van Loo and colleagues provide insights into the action of the anti-inflammatory protein A20. The ZnF7 and ZnF4 ubiquitin-binding domains of A20 are both required to suppress inflammatory signaling and cell death; however, these zinc fingers operate via distinct mechanisms.

Screaton and colleagues describe a protective Zika virus E-dimer-based subunit vaccine engineered to abrogate antibody-dependent enhancement of dengue infection.

NK cells recognize class I and stress-associated ligands. Altfeld and colleagues identify the NK cell receptor NKp44 as directly interacting with the class II HLA-DP in a partially peptide-dependent manner and with functional consequences for NK cell activity.

Dendritic cells (DCs) have been suggested to express a functional NLRP3 inflammasome. Gerlic and colleagues demonstrate, however, that bone marrow–derived DCs completely lack NLRP3 inflammasome activity and that the bulk of splenic DCs lack or have only minimal activity.

Yu and colleagues show that the transcription factor XBP1s positively regulates the cytolytic activity of human NK cells and is required for the IL-15-mediated survival of NK cells.