Issues

Eran Elinav: Beyond the microbiome

Neutrophil NETting ovarian cancer cells in the omentum

The value and social challenges of vaccination.

Keith and Pamer discuss how the bacterial species constituting the intestinal microbiota reduce the host’s susceptibility to enteric infections and describe experimental studies and clinical trials that elucidate new approaches to reducing the risk of infection and transmission of antibiotic-resistant bacteria.

This review provides an overview of the influence of the gut microbiome on host health with a focus on immunomodulation and discusses strategies for manipulating the gut microbiome for the management or prevention of chronic inflammatory conditions.

A role for the gut microbiome in facilitating microglial maturation and shaping microglial physiology has emerged in recent years. This review highlights evidence demonstrating the various mechanisms by which the gut microbiota can influence microglia in both homeostatic and disease conditions.

In recent years, there has been great progress in the field of neuroimmunology, implicating both parenchymal macrophages (microglia) and meningeal immunity in homeostatic brain function. In this review, Norris and Kipnis discuss these two immune compartments and how they are critically segregated to preserve homoeostasis.

An amazing array of tools both old and new are available to investigate the function of astrocytes and microglia. Guttenplan and Liddelow discuss tools available to study the physiology and pathophysiology of these cells both in vivo and in culture systems.

Sorbara et al. report a critical function of the healthy intestinal microbiota in preventing the expansion of antibiotic-resistant Enterobacteriaceae that depends on the production of high levels of short chain fatty acids and an acidic environment to trigger intracellular acidification of Enterobacteriaceae.

Bern et al. demonstrate that acute down-regulation of self-MHC-I in vivo can induce NK cell tolerance to missing-self, depending on the extent of MHC-I deficiency. Additionally, inflammation promotes missing-self reactivity in response to MHC-I down-regulation.

Lauron et al. demonstrate that viral MHCI inhibition within infected cells reduces local antigen-driven generation of resident memory CD8⁺ T cells. Additionally, resident memory CD8⁺ T cells are insufficient in controlling peripheral infection in the context of viral MHCI evasion.

Salou et al. wondered what could differentiate MAIT and NKT cells, if not for TCR specificity. Once split according to RORγt and T-bet–expressing subsets, MAIT and NKT share almost identical transcriptional programs acquired in the thymus, which result in specific tissue residency patterns.

Chen et al. identify Rad21/cohesin as a critical mediator of inflammation/NF-κB–induced differentiation of hematopoietic stem cells (HSCs). Aging-associated increases in inflammation select for HSCs with disrupted or naturally reduced Rad21/cohesin expression exhibiting increased self-renewal and myeloid-biased differentiation: two hallmark features of the aging hematopoietic system.

Metastasis of ovarian cancer frequently involves the omentum and has been described as a passive process that is governed by peritoneal fluid dynamics. Lee et al. show that metastatic tropism of ovarian cancer is actively orchestrated through the induction, by early-stage tumors, of neutrophil influx and chromatin extrusion in the premetastatic omental niche.

This study provides mechanistic insight into how IL-17 receptor adopts EGFR to activate ERK5 axis in Lrig1⁺ stem cells for their proliferation and migration during wounding healing and tumorigenesis.

Greenwald et al. show that VEGF can function as a potent hypoxia-independent inducer of erythropoietin in a population of VSMC-like perivascular stromal cells in a PDGFRβ-dependent manner, thereby expanding erythropoiesis by recruitment of additional cell types to the erythropoietin-producing cell pool.

Naik et al. show that GATA3, Runx1, and E2A are essential for hierarchical assembly of a transcriptionally active RAG locus chromatin hub in CD4⁺CD8⁺ thymocytes. Signal-dependent down-regulation of RAG expression is associated with hub disassembly and depends on Ikaros.