Volume 22 Issue 12, December 2021

Analysis of antibody responses in BCG intravenous vaccination against Mycobacterium tuberculosis in non-human primates show a potential protective role for IgM.

Whether COVID-19 during pregnancy affects the health of children is unclear. Data now show that SARS-CoV-2 infection of mothers can prime the fetal immune response indirectly even when the virus does not infect the fetus.

In patients with rheumatoid arthritis, a short supply of aspartate in the mitochondria can force the endoplasmic reticulum of T cells to generate transmembrane TNF, which in turn contributes to synovial inflammation.

Mitochondria regulate endoplasmic reticulum (ER) size and protein maturation in healthy cells by releasing aspartate, regenerating cytoplasmic NAD⁺ and ADP-ribosylating the ER stress sensor BiP. In the autoimmune disease rheumatoid arthritis, a deficiency in mitochondrial aspartate in T cells causes an increase in ER size and excess production of the inflammatory mediator tumor necrosis factor (TNF), driving tissue inflammation.

The extreme diversity of the human immune system, forged and maintained throughout evolutionary history, provides a potent defense against opportunistic pathogens. Liston and colleagues review the current state of play in the field, identify the key unknowns in the causality of immune variation and identify the multidisciplinary pathways toward an improved understanding.

Many babies have now been born to mothers who were exposed to SARS-CoV-2 during their pregnancy. Here the authors look at the effect of this exposure on the immunology of human neonates, showing immune changes and increased neonatal cytokine responses despite limited evidence of vertical transmission.

Krebs and colleagues identify multiple mAbs that recognize either the RBD or the NTD of SARS-CoV-2 spike protein that have potent cross-neutralizing activities against variants of concern. Combinatorial mAb cocktails have complementary effects on viral neutralization and Fc effector functions and can protect against SARS-CoV-2 escape mutants.

Alter and colleagues show that IgM titers in the plasma and bronchoalveolar lavage fluid represent markers of reduced Mtb burden in rhesus macaques vaccinated intravenously with Bacille Calmette–Guérin.

Snell et al. examine the heterogeneity of CD4⁺ T cells in chronic viral infection, showing that PD-L1 blockade enhances a cytotoxic gene program in antigen-specific T_H1 cells and can restore antiviral CD4⁺ T cell killer function.

Ronchese and colleagues show that IL-13 secreted homeostatically by dermal ILCs contributes to the differentiation of a CD11b^lo type 2 dendritic cell subset, which supports the development of T_H2 cells and curtails the development of T_H17 cells in the skin of mice and humans.

Mitochondrial aspartate regulates ER morphology and co-translational translocation via BiP ADP ribosylation. In T cells from patients with rheumatoid arthritis, mitochondrial aspartate is deficient, resulting in ER expansion and excessive production of the pro-inflammatory cytokine TNF.

Mutations in the RNA-binding proteins Roquin-1 or Regnase-1 cause systemic autoimmunity. Heissmeyer and colleagues show that Roquin-1 and Regnase-1 physically interact and thereby regulate CD4⁺ and CD8⁺ T cell metabolism and functionality.

Haas, Velten and colleagues use single-cell multiomics of human blood and bone marrow to generate a reference map allowing the quantitative linking of cytometry and proteo-genomic information.

Jiang and colleagues describe a high-dimensional, high-throughput tetramer-associated TCR sequencing (TetTCR-SeqHD) method to simultaneously profile TCR sequences, cognate antigen specificities, targeted gene expression and surface-protein expression from tens of thousands of single cells.