ON THE COVER
Adapted from immunofluorescence images from Caielli et al. of neutrophils from lupus patient blood using antibodies against oxidized DNA and outer mitochondrial membrane TOMM20 protein. Lupus neutrophils retain oxidized DNA inside aggregated mitochondria.
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Brief Definitive Report
Genetic functions of the NAIP family of inflammasome receptors for bacterial ligands in mice
Naip knockout mice provide genetic evidence for the specificity of NAIP1, 2, and 5 in recognizing bacterial T3SS needle protein, rod protein, and flagellin, respectively. Naip1−/−, Naip2−/−, and Naip5−/− mice underscore the physiological contribution of the NAIP proteins in innate defense against cytosolic bacteria.
NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo
Vance et al. provide genetic proof for the specificity and essentiality of NAIP proteins for inflammasome responses to specific bacterial ligands in vivo.
TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques
Wang et al. report that TREM2 protects mice from Alzheimer's disease by enabling resident microglia to insulate and alter Aβ plaque structure, thereby limiting neuritic damage.
Rapid in vivo measurement of β-amyloid reveals biphasic clearance kinetics in an Alzheimer’s mouse model
Accumulation of β-amyloid peptide is a key step in Alzheimer’s disease pathogenesis. Yuede et al. propose a novel method to track β-amyloid levels in vivo.
The ETS1 transcription factor is required for the development and cytokine-induced expansion of ILC2
Zook et al. use a novel mouse model to demonstrate a requirement for the transcription factor ETS1 in the development and function of group 2 innate lymphoid cells.
Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus
As an alternative to mitophagy, neutrophils spontaneously extrude mitochondrial (mt) DNA devoid of oxidized residues (Ox). Activated lupus neutrophils or healthy neutrophils treated with IFN/αRNP release ox-mtDNA bound to TFAM, which induces high levels of IFN-α in pDCs.
IFN-γ receptor and STAT1 signaling in B cells are central to spontaneous germinal center formation and autoimmunity
B cell–intrinsic IFN-γ receptor signaling through STAT1 is required for the generation of spontaneous germinal centers, which can lead to pathogenic autoantibody production.
B cell IFN-γ receptor signaling promotes autoimmune germinal centers via cell-intrinsic induction of BCL-6
Jackson et al. propose a role for B cell–intrinsic IFN-γ receptor signaling in spontaneous germinal center activation and autoantibody production.
Continuous inhibitory signaling by both SHP-1 and SHIP-1 pathways is required to maintain unresponsiveness of anergic B cells
Cambier et al. show that the tyrosine phosphatase SHP-1 and the inositol phosphatase SHIP-1 are required to maintain B cell anergy.
A single domain antibody fragment that recognizes the adaptor ASC defines the role of ASC domains in inflammasome assembly
Ploegh et al. raised an alpaca single-domain antibody (VHH) against the inflammasome adaptor ASC. VHHASC blocks inflammasome activation in vitro and in living cells, and demonstrates a role of the ASC CARD domain in cross-linking ASC Pyrin domain filaments.
Killer cell immunoglobulin-like receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition
Rossjohn, Brooks, Vivian, and colleagues provide the most complete picture to date of the impact of KIR3DL1 polymorphism on HLA class I recognition, which can be used to both reevaluate previous work on the involvement of KIR3DL1 in disease as well as inform future disease association studies.
Immune activation of the host cell induces drug tolerance in Mycobacterium tuberculosis both in vitro and in vivo
Russell et al. show that activation of Mycobacterium tuberculosis–infected macrophages in vitro and in vivo enhances drug tolerance and renders the bacilli more refractory to drug-dependent killing.
Dickkopf-related protein 1 (Dkk1) regulates the accumulation and function of myeloid derived suppressor cells in cancer
D’Amico et al. show that Dkk1 exerts immune-suppressive effects by directly targeting β-catenin in murine and human MDSCs and promoting their activation in cancer.
CD1d-restricted peripheral T cell lymphoma in mice and humans
Genestier et al. shed light on the cellular origin of peripheral T cell lymphoma (PTCL), showing that in both mice and humans, unconventional CD1d-restricted T cells may give rise to PTCL.
Gankyrin has an antioxidative role through the feedback regulation of Nrf2 in hepatocellular carcinoma
Yang et al. identify a feedback loop between gankyrin, an oncoprotein overexpressed in human hepatocellular carcinoma (HCC), and Nrf2. The positive feedback modulates a series of antioxidant enzymes that lower intracellular reactive oxygen species to confer protection from mitochondrial damage and cell death.