The immune system actively regulates brain activity through the engagement of immune cells and immunomodulatory molecules. In this issue of Immunity, Klawonn et al. show that the activation of microglia in the striatum triggers an IL-6-mediated autocrine loop and the release of prostaglandins, which in turn induce a negative affective state via the stimulation of medium spiny neurons.

The human lung harbors diverse macrophages that provide barrier immunity and maintain homeostasis, but their precursors are unclear. In this issue of Immunity, Evren et al. use a humanized mouse model to discern that classical monocytes give rise to alveolar and interstitial macrophages, whereas non-classical monocytes contribute to pulmonary intravascular macrophages.

Type 1 innate lymphoid cells (ILC1s) regulate inflammation in the tissues; however, their role in anti-viral immunity remains largely unknown. In this issue of Immunity, Shannon et al. report that ILC1s invoke an anti-viral effect by producing interferon (IFN)γ at homeostasis, thereby limiting viral replication in the oral mucosa.

Substantial variations of tumor immune properties exist among cancer patients, but the contributing factors underlying those variations are poorly understood. In this issue of Immunity, Sayaman et al. uncover associations between germline genetic variants and tumor immune properties, revealing candidate causal genes.

The microbiota impedes pathogen invasion of the intestinal ecosystem, a phenomenon termed colonization resistance. In an upcoming issue of Cell, Stacy et al. describe host-initiated metabolite pathways that functionally alter the microbiota after primary infection, thereby augmenting colonization resistance to subsequent infection.

Immunological memory is a mechanism to protect us against reinfection. Antibodies produced by B cells are integral to this defense strategy and underlie virtually all vaccine success. Here, we explain how B cells memory is generated by infection and vaccination, what influences its efficacy and its persistence, and how characterizing these parameters in the immune response to severe acute respiratory

Astrocytes play both physiological and pathological roles in maintaining central nervous system (CNS) function. Here, we review the varied functions of astrocytes and how these might change in subsets of reactive astrocytes. We review the current understanding of astrocyte interactions with microglia and the vasculature and protective barriers in the central nervous system as well as highlight recent

Heparin, a mammalian polysaccharide, is a widely used anticoagulant medicine to treat thrombotic disorders. It is also known to improve outcomes in sepsis, a leading cause of mortality resulted from infection-induced immune dysfunction. Whereas it is relatively clear how heparin exerts its anticoagulant effect, the immunomodulatory mechanisms enabled by heparin remain enigmatic. Here, we show that

Antibiotics improve clinical outcomes independent of their antibacterial effects. In this issue of Immunity, Almeida et al. and Colaço et al. demonstrate that antibiotic impairment of mitochondrial ribosomes modulates both T-cell-dependent inflammation and host tolerance to infection.

In this issue of Immunity, Hirai et al. illuminate competition for the cytokine TGFβ as a key regulator of CD8+ tissue-resident memory T cell persistence and occupancy in the skin epidermal niche.

Inflammaging is associated with chronic diseases, but tissue-specific changes in the immune system remain unknown. In this issue of Immunity, Mogilenko et al. use single-cell RNA sequencing, flow cytometry, and mass cytometry to describe age-related differences, including the accumulation of age-associated T cells that contribute to inflammaging.

Many studies highlight direct interactions between immune cells and enteric neurons, but whether immune signals can indirectly modulate enteric function through neurotransmitter regulation is poorly understood. In this issue of Immunity, Chen et al. reveal how IL-33 induces intestinal serotonin to promote gut motility.

In a recent issue of Cell, Bowling et al. describe a mechanism by which spliceosome-targeted therapies result in intron-containing transcripts that form double-stranded RNAs (dsRNAs), thereby activating tumor antiviral signaling (viral mimicry) and downstream adaptive immunity.

As the SARS-CoV-2 pandemic has progressed, increasing attention has focused on establishing natural and vaccine-induced immunity against this coronavirus and the disease, COVID-19, that it causes. In this Primer, we explain the fundamental features of T cell memory and their potential relevance for effective immunity to SARS-CoV-2.

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

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

EBF1 is a pioneer transcription factor involved in B lymphocyte specification. In this issue of Immunity, Wang et al. localize EBF1’s pioneering activity to a prion-like domain that mediates recruitment of the nucleosome remodeler Brg1 and FUS-assisted liquid-liquid phase separation.

In this issue of Immunity, Chopp et. al. use single-cell transcriptomics and epigenomics in mice and human samples to delineate developmental trajectories of αβ T cell subsets and refine the kinetic selection model of CD4+ and CD8+ T cell lineage commitment.

Although many immune cells can secrete TGF-β, whether all sources of TGF-β are functionally equivalent is unknown. In this issue, Turner et al. uncover the importance of T regulatory (Treg) cell-intrinsic Tgfb1 gene dose in the prevention of autoimmunity and allergic disease.

Tumors use active immunosuppressive mechanisms to evade immune recognition and shape the local inflammatory environment. In this issue of Immunity, Bonavita et al. report that tumor-derived PGE2 blocks early activation of natural killer cells and interferes with subsequent adaptive immune cell recruitment to the tumor.

Bats harbor diverse viruses and manifest distinct antiviral immune responses. Recently in Cell Host & Microbe, Boys et al. demonstrated that bat receptor transporter protein 4 (RTP4) is an innate antiviral effector that inhibits flavivirus replication, revealing an evolutionary arms race between flaviviruses and their hosts.

Activated B cells participate in either extrafollicular (EF) or germinal center (GC) responses. Canonical responses are composed of a short wave of plasmablasts (PBs) arising from EF sites, followed by GC producing somatically mutated memory B cells (MBC) and long-lived plasma cells. However, somatic hypermutation (SHM) and affinity maturation can take place at both sites, and a substantial fraction