Issues

Randolph and colleagues describe the ontogenic origin and developmental program of a distinct resident peritoneal macrophage population.

Essers et al. find that the extracellular matrix adaptor protein Matrilin-4 confers a resistance to stress stimuli in hematopoietic stem cells.

Drennan et al. use a new mouse to show that A20-deficient NKT cells are hyperresponsive to TCR-dependent stimuli and have severely impaired NKT cell development.

Using a mouse model of Kawasaki disease, Stock and collaborators have discovered an essential role for GM-CSF as an instigator of cardiac inflammation.

Luo et al. report that CXCR2 ligands are responsible for rapid neutrophil mobilization during early-stage acute inflammation and that G-CSF suppresses this mobilization by negatively regulating CXCR2-mediated intracellular signaling.

Adipocyte-specific activation of Notch signaling suppresses lipid metabolism pathways that provide ligands to Pparγ, leading to adipocyte dedifferentiation and development of liposarcomas (LPSs) resembling human dedifferentiated LPSs with complete penetrance. Pparγ ligand supplementation prevents liposarcoma development.

Delbridge, Strasser, and collaborators show that potentially oncogenic RAG1/2-dependent DNA lesions trigger apoptosis through the induction of BIM, which functions as an efficient tumor suppressor.

In a cohort of Zambian heterosexual transmission pairs, the authors show that HIV-1–transmitted variants already exhibit a significant degree of preadaptation to the new host's HLA alleles, which, modulated by polymorphisms that decrease viral fitness, determines early set-point VL and the rate of disease progression in the newly infected individual.

EBV reduces the activation of cytotoxic CD4⁺ effector T cells by inducing a state of reduced immunogenicity in infected B cells. EBV-derived miRNAs suppress release of proinflammatory cytokines, interfere with peptide processing and presentation on HLA class II, repress differentiation of naive CD4⁺ T cells to Th1 cells, and ultimately avoid killing of infected B cells.

Kanneganti and collaborators propose that the lysosomal protease cathepsin B provides a checkpoint for activation of the transcription factor TFEB and lysosomal biogenesis and explore the impact of this pathway on host defense against bacterial infection.

Cha et al. show that Plasmodium GAPDH on the sporozoite surface acts as a ligand for binding Kupffer cell CD68, an interaction that is critical for parasite liver invasion. Thus, Plasmodium GAPDH is a candidate antigen for a prehepatic malaria vaccine.

When inflammasomes trigger pyroptosis, the plasma membrane tears release-soluble cytosolic contents but retains organelles and intracellular bacteria. Neutrophils then efferocytose the pyroptotic cell debris and kill the entrapped bacteria.

Wen et al. show that there are gut microbial antigens sharing significant homology with the host pancreatic protein peptide IGRP and that can drive self-reactive T cell activation and accelerate diabetes in NOD mice.

Geha and collaborators show that IL-23 released by keratinocytes in response to TLR4 ligands stimulates skin DCs to produce IL-23, driving CD4 T cell IL-22 secretion, which causes epidermal thickening.

Cerutti and collaborators show that the humoral arms of the innate and adaptive immune systems are functionally interconnected by pentraxin 3, a soluble pattern recognition receptor that couples innate immune recognition with antibody-inducing function.

Veillette and collaborators generate a mouse model with a deletion spanning the entire 400-kb Slam locus on chromosome 1 to show the overall role of SLAM proteins in NK cell development and function.

Activation of DP1 by PGD₂ in macrophages induces the binding of PRKAR2A to the IFN-γR2 transmembrane region, inhibits JAK2/STAT1 signaling, and triggers the expression of antiinflammatory and reparative genes in myocardial infarction and sepsis.