Host ubiquitination suppresses signaling via the kinase mTOR when macrophages sense the intracellular pathogen Legionella pneumophila. The original image by Stanimir Ivanov shows a macrophage (nucleus in blue) infected with L. pneumophila (green) and host ubiquitin (red) associated with the membrane of the pathogen-occupied vacuole. Artwork by Lewis Long.

Chronic infection with lymphocytic choriomeningitis virus (LCMV) results in moderate immunopathology in wild-type mice. Goldrath and colleagues show that immune responses are progressively attenuated by T cell exhaustion dependent on the HIF pathway (p 1173; News and Views by Göthert, p 1114). Original image by Andrew L. Doedens and Martin H. Stradner is a hematoxylin- and eosin-stained section of mouse lung infected by LCMV in the presence of LCMV-specific T cells with activated HIF.Artwork by Lewis Long.

Immune cells are found in diverse nonlymphoid tissues akin to small residential communities, where they patrol against infection and injury and help to maintain homeostasis. This month's Focus features five specially commissioned Reviews in which interactions and functions of tissueresident leukocytes are discussed. http://www.nature.com/ni/focus/tr_leukocytes/Artwork by Lewis Long

Intestinal immunity to attaching-and-effacing bacterial pathogens requires the local generation of antimicrobial peptides. Murphy and colleagues (p 937; News and Views by Sallusto, p 890) show that a Notch2-dependent subset of classical dendritic cells (cDCs) initiates this response by producing the cytokine IL-23. The original fluorescence micrograph, generated by Ansuman T. Satpathy and Carlos G. Briseño, shows Zbtb46-GFP+ cDCs (green), CD4+ lymphoid cells (pink) and β-catenin-positive epithelial cells (red) in the intestinal mucosa. Artwork by Lewis Long.

Particulate ligands such as cholesterol crystals and amyloid fibrils have been linked to the induction of IL-β in atherosclerosis, Alzheimer's disease and diabetes. Moore and colleagues show that the scavenger receptor CD36 coordinates the intracellular conversion of soluble precursors into crystals or fibrils in the lysosome, which leads to activation of the NLRP3 inflammasome and secretion of IL-1β (p 812; News and Views by Jonathan C. Kagan & Tiffany Horng, p 772). Original confocal fluorescent reflection micrograph by Fred Sheedy and Parisa Kalantari. Artwork by Lewis Long.

A complex resident community of microbes, referred to as the 'commensal microbiota', has coevolved with humans. This month's Focus features a series of specially commissioned articles that discuss the interactions between the microbiota and the immune system and their influence on local and systemic immunological homeostasis. (http://www.nature.com/ni/focus/microbiotaArt work by Lewis Long.

Mast cells mature toward an anaphylaxis-sensitive phenotype. Murakami and colleagues show that PLA2G3, a mammalian homolog of the anaphylactic bee venom phospholipase A2, regulates this process (p 554; News and Views by Philipp Starkl, Thomas Marichal & Stephen J. Galli, p 527). The original image, by Makoto Murakami, is a transmission electron micrograph of a mouse peritoneal mast cell. Artwork by Lewis Long.

Tissue-resident effector memory CD8+ T cells serve as sentinels. Masopust and colleagues (p 509) show that antigen-specific memory cells secrete IFN-γ, eliciting chemokine production to recruit circulating memory cells to the site of reinfection. The original image, by Jason M. Schenkel, is a representative section of the mouse female reproductive tract. Epithelium is stained with anti-cytokeratin (red), and fibroblasts and reticular fibers are stained with anti-ER-TR7 (green). Artwork by Lewis Long.

Antibodies can be carried into the cell during pathogen infection. McEwan and colleagues show that recognition of intracellular antibodies by the cytosolic antibody receptor TRIM21 activates immunological signaling (p 327; News and Views by Teunis B.H. Geijtenbeek & Sonja I. Gringhuis, p 309). Artwork by Lewis Long.

The large number of functional immunoreceptor tyrosine-based activation motifs (ITAMs) in the TCR-CD3 complex is unique among receptors. Vignali and colleagues show that a full complement of ITAMs is required for TCR-driven T cell proliferation, whereas a low number is sufficient for cytokine secretion (p 262). The original image shows CD3 (blue), the metalloprotease ADAM10 (green) and Notch1 (red) in TCR microclusters in stimulated CD4+ T cells. Original image by Clifford Guy and Jamshid Temirov. Artwork by Lewis Long.

Nuclear translocation of NFAT proteins is necessary for gene expression. Serfling and colleagues (p127; News and Views by Macian, p116) show that in pre-TCR–negative thymocytes, IL-7–Jak3–mediated signals result in nuclear localization of NFA Tc1. The original image by Amiya K. Patra shows nuclear NFA Tc2 (yellow, a merge of red (NFA Tc2) and green (DAPI)) in COS-7 cells transfected with a vector expressing NFA Tc2. Artwork by Lewis Long.

The signals that coordinate the navigation of myeloid cells in tissues are incompletely understood. Massberg and colleagues show that NG2+ pericytes control the pattern and efficacy of the interstitial migration of leukocytes (p 41; News and Views by Alon & Nourshargh, p 14). The original confocal microscopy image shows the intracellular localization of the chemoattractant MIF in a resting human pericyte stained in vitro for MIF (red) and F-actin (green). Original image by Konstantin Stark. Artwork by Lewis Long.