Reviews & Analysis

Several studies in 2019 have provided exciting insights into the relationship between the immune response to infection and the host metabolic system.

In this Year in Review, Donna Farber discusses some of the exciting breakthroughs that occurred in the T cell field in 2019, highlighting the therapeutic implications for our understanding of T cell function in infection, allergy, inflammatory disease and cancer.

Organoid technology has emerged as a powerful tool to maintain epithelial cells in a near-native state that can be used to better understand the interactions between epithelial cells and the immune system in tissue development, homeostasis, infection and cancer.

Immune cells and neural cells interact in numerous tissues and organs and can have local and far-reaching physiological effects. Understanding these intimate bidirectional interactions is providing insight into the gut–brain axis, as well as the maternal gut–fetal brain axis.

Here, Marco Colonna and Simone Brioschi highlight several key papers from 2019 that used single-cell and single-nucleus RNA sequencing to provide exciting insights into the neuro-immune interactions that occur in the healthy and diseased brain.

The authors discuss the formation of two main ‘walls’ of B cell memory to protect against pathogen reinfection. The first wall comprises high-affinity antibodies produced by long-lived plasma cells, while the second wall is formed by memory B cells.

Clearing away dead cells — a process known as efferocytosis — is crucial for normal tissue homeostasis and is impaired in several pathological processes. This Review describes new insights into how efferocytes deal with the engulfed dead cell cargo, how efferocytosis supports the resolution of inflammation and how this understanding is informing new therapeutic strategies.

Studies in the field of inflammation in 2019 have highlighted a counterbalancing homeostatic function for the glycolytic metabolite lactate, which is produced in hypoxic conditions, such as in tumours and chronic inflammation. Lionel Ivashkiv describes how lactate suppresses inflammatory signalling pathways and regulates macrophage polarization.

Therapies based on adoptive cellular transfer of regulatory T (T_reg) cells are currently undergoing clinical trials for autoimmune diseases, graft-versus-host disease and the prevention of transplant rejection. This Review provides an overview of T_reg cell biology and discusses the latest approaches to enhance T_reg cells for therapeutic purposes.

In 2019, single-cell sequencing studies provided important insight into the diverse gene expression profiles of tissue macrophages, and new systems for specifically deleting macrophages were reported. A lactate ‘timer’ that controls inflammatory responses in macrophages was also described.

This Review by Handel and colleagues focuses on how simulation modelling can be used to interrogate the immune system. The authors provide an overview of different model types and encourage immunologists to build their own models.

Recent studies using single-cell genomic technologies and in vivo fate mapping have shown that thymic epithelial cells are far more heterogeneous than previously thought, comprising multiple subpopulations with distinct molecular and functional characteristics.

Single-cell sequencing studies in 2019 have led to exciting discoveries relevant to the roles of the immune system in development, homeostasis and disease.

In the past year, researchers have gained a deeper understanding of the interactions between immune cells and microbially derived metabolites. Wendy Garrett describes the new insights into the receptors, immune cells and pathways triggered by microbial metabolites.

Several studies from 2019 have highlighted emerging routes of communication between tissue-resident immune cells and local neurons, stromal cells, endothelial cells and epithelial cells to exert effects beyond the local tissue.

As we age, haematopoiesis becomes skewed towards myelopoiesis. Studies of haematopoietic stem cells (HSCs) transplanted into irradiated recipient mice imply that HSC defects are responsible for this ageing effect. Here, the authors urge caution when using irradiated mice to study haematopoiesis ageing, and propose instead that age-related changes in the bone marrow environment and in downstream progenitors, not just HSCs, may also be responsible for myeloid skewing.

New approaches to vaccine development have generated exciting results over the past 18 months. Focusing on respiratory syncytial virus infection, influenza and tuberculosis, Fauci and Mascola discuss the impact of structure-based vaccine design, gene-based vaccine platforms and advances in adjuvant development.

The gasdermin family of proteins has the capacity to form pores in the membrane, causing a pro-inflammatory lytic type of cell death called pyroptosis, This Review provides a comprehensive overview of the gasdermin family, the mechanisms that control their activation and their role in inflammatory disorders and cancer.

The co-inhibitory receptor TIM3 can serve as a marker of exhausted T cells. Here, the authors investigate the biology of TIM3, discussing its various ligands, signalling pathways and association with human disease. They also provide an overview of emerging clinical data regarding its potential as an anticancer target in combination with PD1 blockade.

This Review focuses on the cytomegaloviruses and the sophisticated strategies they have evolved to evade immune recognition. The authors suggest a better appreciation of these pathways could have clinical implications beyond antiviral immunity, for instance in understanding immune evasion in cancer.