Hayday and colleagues demonstrate that the T cell receptors of a major subset of human colonic intraepithelial γδ T cells mediate specific responses to Butyrophilin-like proteins expressed by human gut epithelial cells. This interaction is conserved in mice, and illustrates the capacity of γδ T cells to make innate and adaptive responses via the single T cell receptor.

Manuscript type (Hayday research article) and DOI 10.1038/s41590-018-0253-5

This month's Focus features a series of specially commissioned articles that discuss the biology of the most important human pathogens today, the characteristics of the immune response and the current strategies to achieve protection. See: https://www.nature.com/collections/infectious-diseases.

TLR3, a sensor of double-stranded RNA, is indispensable for defense against herpes simplex encephalitis. Miyake and colleagues show that the metabolic checkpoint kinase complex mTORC2 is recruited to ligated TLR3 and controls TLR3 responses, including its trafficking along dendrites of neurons. Antibody-mediated potentiation of TLR3 responses in the brain significantly protects mice from herpes simplex encephalitis.

See Miyake et al.

Schwartzberg and colleagues show that a gain-of-function mutant of PI3Kδ drives increased generation of follicular T helper (Tfh) and germinal center (GC) B cells in gut associated lymphoid tissues and peripheral lymphoid organs. While responses to immunization are impaired, activated PI3Kδ promotes self and gut commensal reactivity.

See Schwartzberg et al.

B cells need at least two signals to terminally differentiate into antibody-secreting cells. Pierce and colleagues show that persistent exposure to antigen in the absence of T cell help or ‘pathogen pattern motifs’ leads to B cell death via a calcium-dependent ‘metabolic timer’.

See Pierce et al.

TIGIT is a coinhibitory receptor associated with T cell exhaustion. Tian and colleagues demonstrate that TIGIT is the predominant inhibitory receptor on NK cells in both humans and mice and its blockade enhances NK cell-dependent rejection of tumors in experimental models.

See Tian et al.

McGaha and colleagues show that phagocytosis of apoptotic cells leads to activation of AhR and production of IL-10 in phagocytes, in a manner dependent on DNA recognition.

See Shinde et al.

Meningeal vascular damage accompanies mild traumatic brain injury. McGavern and colleagues report that distinct myeloid cell subsets are temporally recruited to the lesion and are critical for meningeal re-vascularization after such injury.

See Russo et al.

Sander and colleagues show that antigen presenting cells detect bacterial RNA from live bacteria via TLR8 and promote TFH cell differentiation through induction of a specific cytokine profile.

The presentation of antigen by germinal center B cells to follicular T cells engenders the process of antibody affinity maturation and humoral memory. Pierce and colleagues show TLR9 signaling in B cells antagonizes B cell–mediated antigen presentation, which leads to enhanced generation of short-lived plasma cells and production of lower-affinity antibodies.

CD8+ T cell immunosurveillance dynamics influence the outcome of intracellular infections and cancer. Masopust and colleagues show that mucosal tissue–resident memory CD8+ T cells proliferate in situ in response to local antigen and dominate the local recall response.

Plasmacytoid dendritic cells (pDCs) are known for their copious production of type I interferons. Soumelis and colleagues show that functionally and transcriptomically distinct human pDC populations can be generated from a single microbial or cytokine stimulus. Article