Reviews & Analysis

Mitochondria are emerging as important players in innate immunity: they act as signalling platforms for antiviral molecules, produce reactive oxygen species that influence both antiviral and antibacterial immune responses and are a source of factors that initiate sterile inflammation.

Integrins are molecules with dynamic structure that are expressed by all leukocytes. This Review discusses the current knowledge on how these surface molecules integrate intracellular and environmental signals and modify their structure, thereby contributing to the activation and migration of T cells.

Erica Herzog and colleagues put forward the opinion that fibrocytes, a little-studied population of monocyte-derived cells that have properties of both macrophages and fibroblasts, have unique roles in chronic inflammation that warrant further study.

It is well appreciated that sphingosine-1-phosphate (S1P) and its receptors have important roles in controlling lymphocyte migration. This Review discusses the emerging evidence that S1P is involved in other immune responses and considers the clinical implications of this.

Interleukin-7 (IL-7) induces T cell proliferation and enhances antigen-specific immune responses: attributes that pinpoint its value as a potential therapeutic agent. This Review summarizes preclinical and clinical data on the immunorestorative effects of IL-7 in various pathologies and discusses the conditions for which IL-7 therapy might be of use.

This Review describes the anatomical features of the central nervous system (CNS) barriers and focuses on the way in which the immune system responds to neurotropic viruses that establish latent or persistent infections in the CNS. It also discusses imaging technologies that can be used to understand viral entry and antiviral immune responses in the CNS.

Despite the frequently proposed 'redundancy' of the chemokine system, these authors put forward the opinion that targeting a single chemokine receptor can be effective in treating inflammatory disease provided that thein vivopotency is sufficient.

Here, Thomas Boehm considers the commonalities that underlie the adaptive immune systems of jawless and jawed vertebrates, including functionally distinct B- and T-like cells and anatomically segregated sites for their generation, as well somatically diversified and clonally expressed antigen receptors. The features that distinguish the adaptive immune systems in these vertebrate groups are also considered.

The improvement of tuberculosis diagnosis and treatment regimens depends on the identification of suitable biomarkers. Analysis of host immunological markers at diagnosis and throughout treatment may aid new drug development and the clinical management of individual patients.

Platelets are well known as mediators of haemostasis, but their roles in immunity are less well appreciated. Here, the authors relate the diverse immune functions of platelets and discuss how these anucleate cells can promote both innate and adaptive immune responses.

This Review describes how next-generation sequencing has enriched our knowledge of how STAT proteins regulate cytokine-mediated T helper cell differentiation through direct DNA binding and by affecting epigenetic modifications.

This article describes the molecular mechanisms involved in T cell senescence and T cell exhaustion, and proposes that these states are controlled by distinct molecular pathways. Blocking exhaustion rather than senescence may be a safer way to enhance immunity to persistent infections and in ageing.

This Review provides a very accessible summary of the mechanisms of V(D)J recombination, including the role of the chromatin architecture and histone modifications in determining accessibility for RAG (recombination activating gene) protein binding. The authors discuss potential models for RAG specificity and summarize the major outstanding questions in this field.

In this article, Luigina Romani describes the immune mechanisms that have evolved to recognize and respond to fungi. She explains how the failure of either pro-inflammatory or tolerogenic immune responses can lead to the development of fungal diseases.

This Review focuses on how HIV infection affects the functions of dendritic cells and natural killer cells. The authors propose that a better understanding of the roles of these innate immune cells during HIV infection could lead to improved antiviral strategies.

Synergistic and antagonistic signalling crosstalk between receptors of the innate immune system maintains a fine balance between protective immunity and inflammatory pathology. This Review article looks at how pathogens can manipulate this signalling crosstalk to dysregulate the host immune response for their benefit.

Recent studies have shown that caspase 1 activation by inflammasomes controls a set of non-canonical effector mechanisms that might contribute to the immune response during infection and autoimmunity. These mechanisms include unconventional protein secretion, pyroptosis, regulation of metabolic pathways and restriction of bacterial replication.

Here, Wolfgang Junger discusses the importance of purinergic receptor signalling for fine-tuning immune cell responses. Autocrine signalling through purinergic receptors can both amplify and inhibit leukocyte functions; the author explains how this is important for sensing chemotactic gradients and detecting rare antigens.

Toll-like receptors (TLRs) are central to the induction of pro-inflammatory responses, but their signalling pathways must be tightly regulated. As discussed in this article, an emerging level of fine-tuning is mediated by microRNAs, several of which are induced by TLR signalling.

Here the authors describe how multiple pattern recognition receptors, at the host cell surface, in endosomes and in the cytoplasm, are involved in detecting herpesviruses. How do they each contribute to immune defence against the virus, and how does the virus evade this detection and persist in the host?