The last few years have witnessed an increasing body of evidence that challenges the traditional view that immunological memory is an exclusive trait of the adaptive immune system. Myeloid cells can show increased responsiveness upon subsequent stimulation with the same or a different stimulus, well after the initial challenge. This de facto innate immune memory has been termed “trained immunity” and

Immunometabolism has emerged as a key focus for immunologists, with metabolic change in immune cells becoming as important a determinant for specific immune effector responses as discrete signaling pathways. A key output for these changes involves post-translational modification (PTM) of proteins by metabolites. Products of glycolysis and Krebs cycle pathways can mediate these events, as can lipids

Understanding the mechanisms that establish regulatory T (Treg) cell identity is central to understanding Treg cell function. van der Veeken et al. now show that the lineage-determining transcription factor Foxp3 establishes Treg-cell-specific chromatin architecture indirectly, mostly by decreasing the expression of other transcriptional regulators, including TCF1.

The molecular mechanisms that restore microglial quiescence after acute stimulation remain largely unexplored, unlike those that drive microglial activation. In this issue of Immunity, Shemer et al. discover that the microglial IL-10 receptor counteracts the pro-inflammatory effects of TNF to allow restoration of microglial quiescence after peripheral endotoxin challenge.

Allergens induce type-2 immunity, but unresolved questions remain about initiation of this response. In this issue, Perner et al. propose that cutaneous activation of TRPV1+ sensory neurons by protease allergens stimulates release of substance P to induce migration of Th2-skewing CD301b+ DC to draining lymph nodes.

Pre-existing humoral immunity can impact immune responses to heterologous infections. In this issue of Immunity, Wong et al. reveal that memory B cells, while failing to re-enter the germinal center, create an affinity-restricted, diversified B cell repertoire for rapid plasma blast responses. Their findings have important implications to vaccine design.

In Crohn’s disease, the characteristic expansion of mesenteric tissue on sites of intestinal inflammation is known as creeping fat. In a recent issue of Cell, Ha et al. report that translocation of gut bacteria to the mesenteries is associated with the formation of creeping fat.

Understanding the earliest immune responses following HIV infection is critical to inform future vaccines and therapeutics. Here, we review recent prospective human studies in at-risk populations that have provided insight into immune responses during acute infection, including additional relevant data from non-human primate (NHP) studies. We discuss the timing, nature, and function of the diverse

In this issue of Immunity, Wang et al. report isolation of a human antibody derived from volunteers immunized during a malaria vaccine trial. This antibody binds a novel epitope and proves potent at preventing mosquito transmission of the malaria parasite.

In this issue of Immunity, Zeis et al. report the generation of a single-cell atlas of lung innate lymphoid cells (ILCs). Their findings provide insight into the how ILCs are locally maintained, revealing in situ differentiation and diversification as mechanisms of ILC renewal and function.

The contribution of the immunoglobulin E (IgE)-mast cell response to allergy portrays the axis as a villain with malicious intent. A new study from Starkl et al. tells a different story, highlighting a more worthwhile purpose of protecting us against bacterial toxins.

In this issue of Immunity, Weulersse et al. and Braun et al. explain how CD226 expression loss on CD8+ T cells impairs TCR-driven activation, and thereby anti-tumor effector responses, tantamount to taking the CD8+ T cell’s foot off the gas pedal.

The microbiome plays an important role in multiple sclerosis. In a recent issue of Nature, Miyauchi et al. report that gut microbial molecular mimicry in concert with gut microbes that enhance Th17 cells act synergistically to worsen CNS autoimmunity.

Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved T cell subset, which reacts to most bacteria through T cell receptor (TCR)-mediated recognition of metabolites derived from the vitamin B2 biosynthetic pathway. Microbiota-derived signals affect all stages of MAIT cell biology including intra-thymic development, peripheral expansion, and functions in specific organs. In tissues

Although programmed cell death can control intracellular bacterial replication, the role of cell death during systemic Salmonella infection remained elusive. In this issue of Immunity, Doerflinger et al. discover a critical but overlapping role for cell death associated caspases during Salmonella infection.

In this issue of Immunity, Kato et al. show that high-affinity vaccines targeting rare B cells capable of broadly protective antibody responses are not hindered by promotion of terminal plasmacytic differentiation. These findings provide new understanding into vaccine design and offer important insight into B cell fate decisions.

In this issue, Acharya et al. demonstrate that glucocorticoids produced by macrophages and monocytes in the tumor microenvironment induce a dysfunctional CD8+ T cell phenotype. Blocking myeloid glucocorticogenesis enhances tumor immune surveillance and responsiveness to immune checkpoint therapy.

Liver macrophages play critical roles in the pathogenesis of non-alcoholic steatohepatitis (NASH). In this issue of Immunity, Tran et al. and Remmerie et al. reveal that Ly6Chi monocytes in NASH replace dying resident Kupffer cells, while concomitantly are differentiating into distinct lipid associated macrophages.