Current Opinion in Immunology最新文献

The essential and redundant functions of human type I and II interferons (IFNs) have been delineated over the last three decades by studies of patients with inborn errors of immunity or their autoimmune phenocopies, but much less is known about type III IFNs. Patients with cells that do not respond to type III IFNs due to inherited IL10RB deficiency display no overt viral disease, and their inflammatory disease phenotypes can be explained by defective signaling via other interleukine10RB-dependent pathways. Moreover, patients with inherited deficiencies of interferon-stimulated gene factor 3 (ISGF-3) (STAT1, STAT2, IRF9) present viral diseases also seen in patients with inherited deficiencies of the type I IFN receptor (IFNAR1/2). Finally, patients with autoantibodies neutralizing type III IFNs have no obvious predisposition to viral disease. Current findings thus suggest that type III IFNs are largely redundant in humans. The essential functions of human type III IFNs, particularly in antiviral defenses, remain to be discovered.

Lambda interferons (IFNλs), also termed type III interferons (IFNs) or interleukins-28/29, have been in the shadow of type I IFNs for a long time. Their common induction mechanisms and signalling cascades with type I IFNs have made difficult the unwinding of their unique nonredundant functions. However, this is now changing with mounting evidence supporting a major role of IFNλs as a specialized antiviral defense system in the body, mediating protection at mucosal barrier surfaces while limiting immunopathology.

Here, we review the latest progress on the complex activities of IFNλs in the respiratory tract, focusing on their multiple effects in IFNλ receptor-expressing cells, the modulation of innate and adaptive immune responses in the context of infections and respiratory diseases, and their similarities and differences with type I IFNs. We also discuss their potential in therapeutic applications and the most recent developments in that direction.

Effective high-affinity, long-term humoral immunity requires T cell help provided by a subset of differentiated CD4⁺ T cells known as T follicular helper (Tfh) cells. Classically, Tfh cells provide contact-dependent help for the generation of germinal centers (GCs) in secondary lymphoid organs (SLOs). Recent studies have expanded the conventional definition of Tfh cells, revealing new functions, new descriptions of Tfh subsets, new factors regulating Tfh differentiation, and new roles outside of SLO GCs. Together, these data suggest that one Tfh is not equivalent to another, helping redefine our understanding of Tfh cells and their biology.

Interferons (IFNs) are an integral component of the host innate immune response during viral infection. Recent advances in the study of type I and III IFNs suggest that though both types counteract viral infection, type III IFNs act predominantly at epithelial barrier sites, while type I IFNs drive systemic responses. The dynamics and specific roles of type I versus III IFNs have been studied in the context of infection by a variety of enteric pathogens, including reovirus, rotavirus, norovirus, astrovirus, and intestinal severe acute respiratory syndrome coronavirus 2, revealing shared patterns of regulatory influence. An important role for the gut microbiota, including the virome, in regulating homeostasis and priming of intestinal IFN responses has also recently emerged.

The composition and quantity of food we eat have a drastic impact on the development and function of immune responses. In this review, we highlight defined nutritional interventions shown to enhance antitumor immunity, including ketogenic, low-protein, high-fructose, and high-fiber diets, as well as dietary restriction. We propose that incorporating such nutritional interventions into immunotherapy protocols has the potential to increase therapeutic responsiveness and long-term tumor control in patients with cancer.

Type I and III interferons (IFN-I and IFN-III) have a central role in the early antimicrobial response against invading pathogens. Induction of IFN-Is and IFN-IIIs arises due to the sensing by pattern recognition receptors of pathogen-associated molecular patterns (from micro-organisms) or of damage-associated molecular patterns (DAMPs; produced by host cells). Here, we review recent developments on how IFN-I and IFN-III expression is stimulated by different pathogens and how the signalling pathways leading to IFN induction are tightly regulated. We also summarise the growing knowledge of the sensing pathways that lead to IFN-I and IFN-III induction in response to severe acute respiratory syndrome coronavirus 2.

In this review, we provide an overview of the intricate host–virus interactions that have emerged from the study of SARS-CoV-2 infection. We focus on the antiviral mechanisms of interferon-stimulated genes (ISGs) and their modulation of viral entry, replication, and release. We explore the role of a selection ISGs, including BST2, CD74, CH25H, DAXX, IFI6, IFITM1–3, LY6E, NCOA7, PLSCR1, OAS1, RTP4, and ZC3HAV1/ZAP, in restricting SARS-CoV-2 infection and discuss the virus’s countermeasures. By synthesizing the latest research on SARS-CoV-2 and host antiviral responses, this review aims to provide a deeper understanding of the antiviral state of the cell under SARS-CoV-2 and other viral infections, offering insights for the development of novel antiviral strategies and therapeutics.

The maturation of B cells within the germinal centre (GC) is necessary for antigen-specific immune responses and memory. Dysfunction in the GC can lead to immunodeficiencies, autoimmune diseases, or lymphomas. Here we describe how recent advances in single-cell and spatial genomics have enabled new discoveries about the diversity of human GC B cell states. However, with the advent of these hypothesis-generating technologies, the field should now transition towards testing bioinformatic predictions using experimental models of the human GC. We review available experimental culture systems for modelling human B cell responses and discuss the potential limitations of different methods in capturing bona fide GC B cell states. Together, the combination of cell atlas–based mapping with experimental modelling of lymphoid tissues holds great promise to better understand the maturation of human B cells in the GC response and generate new insights into human immune health and disease.

Type I and type III interferons (IFNs) are major components in activating the innate immune response. Common to both are two distinct receptor chains (IFNAR1/IFNAR2 and IFNLR1/IL10R2), which form ternary complexes upon binding their respective ligands. This results in close proximity of the intracellularly associated kinases JAK1 and TYK2, which cross phosphorylate each other, the associated receptor chains, and signal transducer and activator of transcriptions, with the latter activating IFN-stimulated genes. While there are clear similarities in the biological responses toward type I and type III IFNs, differences have been found in their tropism, tuning of activity, and induction of the immune response. Here, we focus on how these differences are embedded in the structure/function relations of these two systems in light of the recent progress that provides in-depth information on the structural assembly of these receptors and their functional implications and how these differ between the mouse and human systems.