Volume 22 Issue 5, May 2021

A systems immunology analysis of controlled human malaria infections in Africans who were malaria experienced and Europeans who were malaria naive yields new insights into old questions of malaria immunity.

T cell responses probably play important roles in the control of SARS-CoV-2 infection, but they have been relatively understudied. Data now suggest that the majority of infected individuals develop robust and long-lasting T cell immunity, which has implications for the durability of immunity and future vaccine approaches.

Single-cell technologies reveal the building blocks of secondary lymphoid organs, identifying Grem1⁺ fibroblastic reticular cells (FRCs) as critical niche cells that contribute to resident dendritic cell homeostasis and T cell immunity.

The TAM receptor kinases Axl and Mer are critical for microglial recognition and clearance of accumulating amyloid in transgenic models of Alzheimer’s disease.

The Global Thymus Network convened virtually for ThymUS 2020 on 3–4 November 2020. Participants shared recent advances in thymus biology and enjoyed a reprieve from 2020 stressors.

The NLRP3 inflammasome is a central operator in inflammation. Sharma and Kanneganti review the varied roles played by the NLRP3 inflammasome in cancer and metabolic diseases.

Extracellular vesicles (EVs) can exert potent immunomodulatory effects. Wirtz and colleagues review the types of EV and their influence on tumor responses.

Fibroblastic reticular cells (FRCs) provide structural support and soluble factors necessary for proper lymph node organization and function. Turley and colleagues use scRNA-seq to identify a unique Gremlin1-expressing FRC subset that is found in T cell zones. Grem1⁺ FRCs support the survival of resident cDCs and are necessary to promote T cell immunity.

How microglia sense amyloid plaques in Alzheimer’s disease has remained mysterious. Lemke and colleagues report that TAM receptor kinases are absolutely required for normal microglial recognition of, response to and phagocytosis of Aβ plaques. Surprisingly, TAM-mediated microglial phagocytosis of Aβ material does not constrain, but rather promotes, the formation of dense-core plaques.

Tumor-associated macrophages (TAMs) play multifaceted roles in establishing an immunosuppressive tumor microenvironment. Sica and colleagues find that macrophage-intrinsic complement signaling initiates a pathway leading to the induction of highly tumorigenic TAMs.

FOXP3 deficiency leads to dramatic loss of immune homeostasis. This multicenter collaborative group finds that loss of FOXP3 function only disrupts a few core genes, but this unmasks a degree of systemic inflammation, and it is this environment that then strongly perturbs T_reg cells.

The contribution of T cells to the SARS-CoV-2 response remains an important and unresolved question. Moss and colleagues examine T cell and antibody kinetics in a large cohort of patients with COVID-19 and find robust and durable T cell responses.

Sun and colleagues provide a new resource, multi-omics analysis of NK cell Jak–STAT signaling in response to the cytokines IL-2, IL-15, IL-12, IL-18 and IFN-α, showing synergistic and antagonistic interactions that govern NK cell activity.

Immune cells exert important effects on white adipose tissue (WAT) in metabolic diseases. O’Sullivan and colleagues generate a comprehensive single-cell atlas of WAT cells in both health and disease to identify new cellular networks and differentiation trajectories.

Malaria immunity can be acquired through natural infection, but the correlates of protection are still being determined. Yazdanbakhsh and colleagues combine experimental infection of volunteers with Plasmodium falciparum with systems analysis to throw light on the nature of protective immune responses.