December 2016 | Volume 213, No. 13
- What does PD-L1 positive or negative mean?
Ribas and Hu-Lieskovan show that different processes may lead to the expression of PD-L1 on cancer cells, and each one of them may have a different meaning to interpret the results of clinical trials with anti–PD-1/L1 antibodies.
Brief Definitive Reports
- The common mouse protozoa Tritrichomonas muris alters mucosal T cell homeostasis and colitis susceptibility
Escalante et al. show that a highly prevalent mouse intestinal protozoa, Tritrichomonas muris, was found to be a confounding factor in murine colitis. Mice infected with this parasite had elevated baseline levels of Th1 cytokines and developed exacerbated Th1-mediated disease.
- NLRP2 controls age-associated maternal fertility
Kuchmiy et al. show that Nlrp2, while dispensable for regulation of inflammasome activation, controls maternal fertility with progressing age, playing an unexpected and critical role in maintaining oocyte quality later in life.
- Human dendritic cells (DCs) are derived from distinct circulating precursors that are precommitted to become CD1c+ or CD141+ DCs
Breton et al. identify CD172a as a lineage marker that distinguishes human cDC precursor (pre-cDC) subpopulations committed to the CD1c+ lineage (CD172a+ pre-cDCs) or CD141+ lineage (CD172a− pre-cDCs).
- RAB43 facilitates cross-presentation of cell-associated antigens by CD8α+ dendritic cells
RAB43 is a vesicular transport protein unique to CD8α+ DCs that is localized to the Golgi. Kretzer et al. show that RAB43 is necessary for optimal cross-presentation of cell-associated antigens by CD8α+ DCs in vitro and in vivo but that it is dispensable for cross-presentation by in vitro monocyte-derived DCs.
- Mycolactone subverts immunity by selectively blocking the Sec61 translocon
Baron et al. show that mycolactone, an immunosuppressive macrolide produced by the pathogen Mycobacterium ulcerans, operates by targeting the Sec61 translocon. This identifies the most potent Sec61 inhibitor reported to date and the potential of inhibiting Sec61 for immune modulation.
- Tissue-specific programming of memory CD8 T cell subsets impacts protection against lethal respiratory virus infection
Abboud et al. reveal the striking and unexpected spatial organization of central- versus effector-like memory cells within the infected lung tissue and how cooperation between these two subsets contributes to host defense.
- Dampened antiviral immunity to intravaginal exposure to RNA viral pathogens allows enhanced viral replication
Khan et al. demonstrate that the lower female reproductive tract is exceptionally vulnerable to infection by LCMV and Zika virus, as intravaginal exposure to these RNA viral pathogens elicits a dampened antiviral immune response.
- Interferon regulatory factor 2 protects mice from lethal viral neuroinvasion
Li et al. describe a novel role for IRF2, previously known as a negative regulator of type I IFN signaling, in protection of mice from lethal viral neuroinvasion by facilitating the proper localization of B cells and antibodies to the central nervous system.
- Dorsal horn interneuron-derived Netrin-4 contributes to spinal sensitization in chronic pain via Unc5B
Hayano et al. show that Netrin-4, which is originally identified as an axon guidance molecule, is capable of enhancing sensitivity to sensory input and can contribute to neuropathic pain. The findings provide evidence for a previously unknown pain-inducing signal from spinal cord interneurons.
- Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tumor-initiating cells
Chan et al. report that treatment of tumor-bearing mice with low-dose metronomic chemotherapy prevents stromal secretion of ELR+ chemokines and induction of tumor-initiating cells usually observed with administration of drugs at maximum tolerated dose.
- Modeling synovial sarcoma metastasis in the mouse: PI3′-lipid signaling and inflammation
Barrott et al. show that PI3′-lipid signaling potentiates metastasis in a genetically engineered mouse model of synovial sarcomagenesis and drives cancer cells to express CSF1, recruiting macrophages to the tumor microenvironment.
- Early generated B1 B cells with restricted BCRs become chronic lymphocytic leukemia with continued c-Myc and low Bmf expression
Hayakawa et al. show that distinctive B-lineage progression from B-1 development allows for generation of B1a cells with restricted BCRs and self-renewal capacity, both contributing to potential for CLL progression.
- STAT1 regulates marginal zone B cell differentiation in response to inflammation and infection with blood-borne bacteria
Chen et al. show that STAT1 positively regulates TLR- and S. pneumoniae–induced IgM responses of MZ B cells through up-regulation of Prdm1 expression, and STAT1 is crucial for MZ B cell–mediated clearance of blood-borne S. pneumoniae infection.
- Systemic toxoplasma infection triggers a long-term defect in the generation and function of naive T lymphocytes
Kugler et al. show that systemic infection with Toxoplasma gondii triggers a long-term impairment in thymic function, which leads to an immunodeficient state reflected in decreased antimicrobial resistance.
- Specific niches for lung-resident memory CD8+ T cells at the site of tissue regeneration enable CD69-independent maintenance
Takamura et al. show that most lung CD8+ TRM cells are not maintained in the inducible bronchus-associated lymphoid tissue (iBALT) but are maintained in specific niches created at the site of tissue regeneration, which are termed as repair-associated memory depots (RAMDs).
- Antigen-dependent competition shapes the local repertoire of tissue-resident memory CD8+ T cells
Muschaweckh et al. show that antigen presentation in the skin regulates the generation of tissue-resident memory T (TRM) cells by orchestrating local competition of antiviral CD8+ T cells, revealing a mechanism to fine-tune the repertoire of regional pools of TRM cells.