Issues

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Takamura et al. show that most lung CD8⁺ T_RM 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).

Muschaweckh et al. show that antigen presentation in the skin regulates the generation of tissue-resident memory T (T_RM) cells by orchestrating local competition of antiviral CD8⁺ T cells, revealing a mechanism to fine-tune the repertoire of regional pools of T_RM cells.