- PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity
Both tumor- and host-derived PD-L1 can play critical roles in immunosuppression; differences in tumor immunogenicity appear to underlie their relative contributions. Juneja et al. show that in immunogenic MC38 tumors, PD-L1 on tumor cells dominates in suppressing tumor immunity by inhibiting CD8 T cell cytotoxicity.
- ZMPSTE24 defends against influenza and other pathogenic viruses
Fu et al. show that ZMPSTE24 is a broad-spectrum antiviral protein that inhibits entry of selected fusogenic viruses by functioning as an effector in the IFITM pathway. ZMPSTE24 protease activity is dispensable for viral restriction. In mice, ZMPSTE24 deficiency increases susceptibility to influenza infection.
- Autonomous TNF is critical for in vivo monocyte survival in steady state and inflammation
Using in vivo experimentation and an in vitro microfluidic system, Wolf et al. demonstrate that monocytes require low levels of self-made TNF for their survival, both during monopoiesis and under specific immune challenges. They highlight the significance of this autonomous mechanism in a mouse multiple sclerosis model in which TNF-deficient monocytes survive less in the inflamed spinal cord, resulting in delayed disease onset.
- HIV: Persistence through division
A long-lived latent reservoir for HIV-1 persists in CD4+ T cells despite antiretroviral therapy and is the major barrier to cure. In this issue of JEM, Hosmane et al. show that T cell proliferation could explain the long-term persistence of this reservoir.
- Living in an adaptive world: Genomic dissection of the genus Homo and its immune response
Quach and Quintana-Murci review the genetic and evolutionary history of our species, including how natural selection has shaped human genome diversity, and discuss the added value of population and functional genomic approaches in settings relevant to immunity and infection.
- Differentiation of germinal center B cells into plasma cells is initiated by high-affinity antigen and completed by Tfh cells
Kräutler et al. show that differentiation of antibody-producing plasma cells from germinal center (GC) B cell precursors is initiated by direct contact with high-affinity antigen within the GC but completed by separate signals delivered by collaborating, GC-resident T follicular helper cells.
- BATF2 inhibits immunopathological Th17 responses by suppressing Il23a expression during Trypanosoma cruzi infection
Kitada et al. demonstrate that transcription factor BATF2 induced by IFN-γ in macrophages and dendritic cells prevents Th17-mediated multiorgan pathology through suppression of IL-23 production during T. cruzi infection.
- TLR4 signals in B lymphocytes are transduced via the B cell antigen receptor and SYK
Schweighoffer et al. demonstrate that in B cells, TLR4 transduces signals through two distinct pathways: one via the BCR to the activation of SYK, ERK, and AKT and the other via MYD88 to the activation of NF-κB.
- The kinase TBK1 functions in dendritic cells to regulate T cell homeostasis, autoimmunity, and antitumor immunity
Xiao et al. demonstrate that a protein kinase, TBK1, regulates the function of dendritic cells in mediating immune responses.
- Liver carcinogenesis by FOS-dependent inflammation and cholesterol dysregulation
Hepatocellular cancers arise in a background of liver damage and inflammation. Bakiri et al. describe the function of the transcription factor c-Fos/AP-1 using mouse models and human data. c-Fos affects cholesterol and bile acid metabolism and induces DNA damage and inflammation, thus promoting liver cancer.