Trends in Immunology最新文献

A genealogy of immunity reveals increasingly complex systems for pathogen response, organism homeostasis, and multispecies interaction. New studies show how the five senses can all contribute to behavioral, shared and population level immunity redefining our understanding of the ways organisms communicate among and defend themselves.

In the germinal center (GC), B cells undergo rounds of somatic hypermutation (SHM), proliferation, and positive selection to develop into high-affinity, long-lived plasma cells and memory B cells. It is well established that, upon activation, B cells significantly alter their metabolism, but until recently little was understood about their metabolism within the GC. In this review we discuss novel in vivo models in which GC B cell (GCBC) metabolism is disrupted; these have greatly increased our understanding of B cell metabolic phenotype. GCBCs are unusual in that, unlike almost all other rapidly proliferating immune cells, they use little glycolysis but prefer fatty acid oxidation (FAO) to fuel ATP synthesis, whilst preferentially utilizing glucose and amino acids as carbon and nitrogen sources for biosynthetic pathways.

Various mammalian CD8⁺ T cell subsets with regulatory properties are either formed through a thymus-dependent mechanism or induced under various experimental protocols and referred to as CD8⁺ regulatory T cells (Tregs). CD8⁺ Tregs maintain distinct functions in the presence of CD4⁺ Tregs. This review focuses on the Foxp3⁺CD8⁺ Treg subset, which is typically extremely rare in unmanipulated mice and healthy humans under steady-state conditions. However, they can be induced and expanded for transplantation, autoimmune diseases, cancer, viral infections, and T cell receptor transgenic adoptive cell transfer models. Here, we summarize recent research progress related to this population, including the identification of phenotypic markers, induction determinants, and functional activities. Additionally, we discuss advances in manipulating Foxp3⁺CD8⁺ Tregs in autoimmunity and transplantation.

The devastating impact of respiratory infections demonstrates the critical need for novel prophylactic vaccines. In this opinion article, we advocate for bacterial immunotherapies as a complementary tool in our fight against respiratory infections. These immunotherapies can activate a wide spectrum of immunological mechanisms, with trained immunity (TI) being particularly significant. This phenomenon has led to the concept of trained immunity-based vaccines (TIbVs), which represent a novel approach in vaccinology. We discuss examples of TIbVs, including the tuberculosis vaccine Bacille Calmette-Guérin (BCG) and the polybacterial immunotherapy MV130. From our viewpoint, illustrating the mode of action and clinical evidence supports the proposal that TIbVs should be considered as next-generation vaccines to confer protection against a wide range of respiratory infections.

Supporting emerging immunologists in Latin America and the Caribbean (LAC) is crucial amidst fragile funding and policy shifts in the region. Their growth can deliver region-specific health solutions, foster pandemic preparedness, and advance neglected tropical disease research, paying it forward to reduce health inequities and drive global scientific progress.

IFN-γ is a pleiotropic antiviral cytokine that coordinates innate and adaptive immune responses and induces both immunostimulatory and immunosuppressive activities, limiting its use in the clinic. Due to its antiviral role, several viruses express proteins that bind IFN-γ, blocking its interaction with the IFN-γ receptor (IFNGR). However, varicella zoster virus glycoprotein C binds IFN-γ and induces the expression of a subset of specific ISGs, similar to biased IFN-γ agonists generated based on the crystal structure of the IFN-γ - IFNGR complex. Here, we propose using structural and mechanistic information from viral proteins and biased agonists to design novel IFN-γ agonists that fine-tune IFN-γ - IFNGR activity, reducing the immunosuppressive and toxic effects of this cytokine.

Microglia, key orchestrators of the brain's immune responses, play a pivotal role in the progression of Alzheimer's disease (AD). Emerging human models, including stem cell-derived microglia and cerebral organoids, are transforming our understanding of microglial contributions to AD pathology. In this review, we highlight how these models have uncovered human-specific microglial responses to amyloid plaques and their regulation of neuroinflammation, which are not recapitulated in animal models. We also illustrate how advanced human models that better mimic brain physiology and AD pathology are providing unprecedented insights into the multifaceted roles of microglia. These innovative approaches, combined with sophisticated technologies for cell editing and analysis, are shaping AD research and opening new avenues for therapeutic interventions targeting microglia.

Cancer is increasingly prevalent worldwide, often coexisting with type 2 diabetes (T2D). Recent breakthroughs reveal the immune system's pivotal role in eliminating tumors and how the metabolic environment, such as glucose availability, affects antitumor immunity. Diabetes is known to dysregulate both innate and adaptive immune responses, while cancer creates an immunosuppressive microenvironment. We hypothesize that diabetes in cancer subjects may exacerbate this immunosuppression. Here, we examine the current understanding of the interplay between T2D and solid tumors and the associated challenges. Despite inconsistencies in data from mouse models and human tissues, evidence suggests that T2D can impact the antitumor response. Possible mechanisms may involve myeloid cells, inducing local immunosuppression and impairing antigen presentation, and certain lymphoid cell populations, exhibiting exhaustion.

The ongoing evolution of SARS-CoV-2 poses significant challenges to existing neutralizing antibodies and vaccines through immune escape mutations. By leveraging genomic surveillance and antibody deep mutational scanning (DMS) data, Raharinirina and colleagues developed a computational framework to elucidate region-specific SARS-CoV-2 variant dynamics and predict evolutionary trends under population immunity.

The mammalian inflammasome is crucial for responding to environmental/intrinsic stress, and its regulation remains a significant focus in immune-mediated inflammatory diseases and antitumor immunity. Recent studies highlight a close link between palmitoylation and inflammasome regulation. However, this type of regulation remains elusive but may harbor potential for combating inflammation-driven disorders.