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Molecular mechanisms connecting the gut-brain axis to immunity remain elusive. In this issue of Immunity, Labed et al. (2018) demonstrate that two evolutionarily conserved signaling mechanisms, the neuronal muscarinic and the epithelial Wnt pathways, together induce antimicrobial peptide expression that protects Caenorhabditis elegans against intestinal infection.
To obtain a molecular definition of regulatory T (Treg) cell identity, we performed proteomics and transcriptomics on various populations of human regulatory and conventional CD4+ T (Tconv) cells. A protein expression signature was identified that defines all Treg cells, and another signature that defines effector Treg cells. These signatures could not be extrapolated from transcriptome data. Unique...
Antiretroviral therapy can effectively block HIV-1 replication and prevent or reverse immunodeficiency in HIV-1-infected individuals. However, viral replication resumes within weeks of treatment interruption. The major barrier to a cure is a small pool of resting memory CD4+ T cells that harbor latent HIV-1 proviruses. This latent reservoir is now the focus of an intense international research effort...
The development of T cell tolerance in the thymus requires the presentation of host proteins by multiple antigen-presenting cell (APC) types. However, the importance of transferring host antigens from transcription factor AIRE-dependent medullary thymic epithelial cells (mTECs) to bone marrow (BM) APCs is unknown. We report that antigen was primarily transferred from mTECs to CD8α+ dendritic cells...
TREM2 is known for its role in microglial phagocytosis and in neurodegenerative diseases. In this issue of Immunity, Filipello et al. (2018) show that microglial TREM2 is required for synaptic pruning in early development. TREM2-deficient mice show altered social behavior in adulthood, linking TREM2 to neurodevelopmental disease.
Exhausted CD8 T (Tex) cells are immunotherapy targets in chronic infection and cancer, but a comprehensive assessment of Tex cell diversity in human disease is lacking. Here, we developed a transcriptomic- and epigenetic-guided mass cytometry approach to define core exhaustion-specific genes and disease-induced changes in Tex cells in HIV and human cancer. Single-cell proteomic profiling identified...
Regulated antimicrobial peptide expression in the intestinal epithelium is key to defense against infection and to microbiota homeostasis. Understanding the mechanisms that regulate such expression is necessary for understanding immune homeostasis and inflammatory disease and for developing safe and effective therapies. We used Caenorhabditis elegans in a preclinical approach to discover mechanisms...
Dietary fiber protects against chronic inflammatory diseases by dampening immune responses through short-chain fatty acids (SCFAs). Here we examined the effect of dietary fiber in viral infection, where the anti-inflammatory properties of SCFAs in principle could prevent protective immunity. Instead, we found that fermentable dietary fiber increased survival of influenza-infected mice through two...
Innate immune training is a recently described mechanism that allows innate cells to recollect a previous inflammatory episode. In a recent issue of Nature, Wendeln et al. (2018) show that peripheral inflammation can alter long-term microglia function, influencing neuropathology later in life.
Infections are thought to trigger CD8+ cytotoxic T lymphocyte (CTL) responses during autoimmunity. However, the transcriptional programs governing the tissue-destructive potential of CTLs remain poorly defined. In a model of central nervous system (CNS) inflammation, we found that infection with lymphocytic choriomeningitis virus (LCMV), but not Listeria monocytogenes (Lm), drove autoimmunity. The...
In this issue of Immunity, Trompette et al. (2018) show that dietary fiber and short chain fatty acids reduce influenza A virus-associated immunopathology by enhancing CD8+ T cell effector function and by promoting the differentiation of alternatively activated macrophages.
HIV-1 vaccine development has been stymied by an inability to induce broadly reactive neutralizing antibodies to the envelope (Env) trimer, the sole viral antigen on the virion surface. Antibodies isolated from HIV-1-infected donors, however, have been shown to recognize all major exposed regions of the prefusion-closed Env trimer, and an emerging understanding of the immunological and structural...
Neutrophil recruitment in response to pathogen invasion is mediated through “self” tissue damage signals (DAMPs) and pathogen associated signals (PAMPs). In this issue of Immunity, Huang and Niethammer, (2018) demonstrate that DAMP signaling is a prerequisite for neutrophil recruitment.
Intestinal infection triggers potent immune responses to combat pathogens and concomitantly drives epithelial renewal to maintain barrier integrity. Current models propose that epithelial renewal is primarily driven by damage caused by reactive oxygen species (ROS). Here we found that in Drosophila, the Imd-NF-κB pathway controlled enterocyte (EC) shedding upon infection, via a mechanism independent...
It is assumed that collateral damage from the immune system drives intestinal epithelial cell (IEC) expulsion during enteric infections. In this issue of Immunity, Zhai et al. (2018) describe how Drosophila’s canonical immune deficiency (Imd) pathway programs IEC delamination in the gut.
The triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial innate immune receptor associated with a lethal form of early, progressive dementia, Nasu-Hakola disease, and with an increased risk of Alzheimer’s disease. Microglial defects in phagocytosis of toxic aggregates or apoptotic membranes were proposed to be at the origin of the pathological processes in the presence of Trem2...
Biomedical interventions to curb malaria-causing Plasmodium falciparum (Pf) infections are critically needed. Two studies in Nature Medicine, Kisalu et al. (2018) and Tan et al. (2018), report the isolation of potent human antibodies that target a new epitope on Pf sporozoites and mediate effective parasite inhibition in pre-clinical models.
Tissue damage and infection are deemed likewise triggers of innate immune responses. But whereas neutrophil responses to microbes are generally protective, neutrophil recruitment into damaged tissues without infection is deleterious. Why neutrophils respond to tissue damage and not just to microbes is unknown. Is it a flaw of the innate immune system that persists because evolution did not select...
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