Mucosal surfaces provide a remarkably effective barrier against potentially dangerous pathogens. Therefore, enhancing mucosal immunity through vaccines-strengthening that first line of defense-holds ...significant promise for reducing the burden of viral diseases. The large and varied class of viral pathogens, however, continues to present thorny challenges to vaccine development. Two primary difficulties exist: Viruses exhibit a stunning diversity of strategies for evading the host immune response, and even when we understand the nature of effective immune protection against a given virus, eliciting that protection is technically challenging. Only a few mucosal vaccines have surmounted these obstacles thus far. Recent developments, however, could greatly improve vaccine design. In this review, we first sketch out our understanding of mucosal immunity and then compare the herpes simplex virus, human immunodeficiency virus, and influenza virus to illustrate the distinct challenges of developing successful vaccines and to outline potential solutions.
Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Without approved antiviral therapeutics or vaccines to this ongoing ...global threat, type I and type III interferons (IFNs) are currently being evaluated for their efficacy. Both the role of IFNs and the use of recombinant IFNs in two related, highly pathogenic coronaviruses, SARS-CoV and MERS-CoV, have been controversial in terms of their protective effects in the host. In this review, we describe the recent progress in our understanding of both type I and type III IFN-mediated innate antiviral responses against human coronaviruses and discuss the potential use of IFNs as a treatment strategy for COVID-19.
Type I and type III interferons are potent antiviral cytokines with non-redundant functions. Park and Iwasaki review the protective versus pathogenic roles of type I and type III interferons in highly pathogenic coronavirus infections and discuss the prophylactic and therapeutic potential of these interferons in the current COVID-19 pandemic.
The internal surfaces of the human body are covered by distinct types of epithelial cells and mucus-secreting cells. The mucosal surfaces serve many vital functions, such as respiration (nasal ...passage and lung), absorption (gastrointestinal tract), excretion (lung, urinary tract, large intestine), and reproduction (reproductive tract). In performing these functions, the host is inevitably exposed to environmental antigens, food particles, commensal flora, and pathogens. Mucosal surfaces contain specialized dendritic cells (DCs) capable of sensing these external stimuli and mounting appropriate local responses depending on the nature of the elements they encounter. In the absence of pathogens, mucosal DCs either ignore the antigen or induce regulatory responses. Upon recognition of microorganisms that invade the mucosal barrier, mucosal DCs mount robust protective immunity. This review highlights progress in our understanding of how mucosal DCs process external information and direct appropriate responses by mobilizing various cells of the innate and adaptive immune systems to achieve homeostasis and protection.
Since the initial reports of a cluster of pneumonia cases of unidentified origin in Wuhan, China, in December 2019, the novel coronavirus that causes this disease - severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2) - has spread throughout the world, igniting the twenty-first century's deadliest pandemic. Over the past 12 months, a dizzying array of information has emerged from numerous laboratories, covering everything from the putative origin of SARS-CoV-2 to the development of numerous candidate vaccines. Many immunologists quickly pivoted from their existing research to focus on coronavirus disease 2019 (COVID-19) and, owing to this unprecedented convergence of efforts on one viral infection, a remarkable body of work has been produced and disseminated, through both preprint servers and peer-reviewed journals. Here, we take readers through the timeline of key discoveries during the first year of the pandemic, which showcases the extraordinary leaps in our understanding of the immune response to SARS-CoV-2 and highlights gaps in our knowledge as well as areas for future investigations.
Microbial infections are recognized by the innate immune system both to elicit immediate defense and to generate long-lasting adaptive immunity. To detect and respond to vastly different groups of ...pathogens, the innate immune system uses several recognition systems that rely on sensing common structural and functional features associated with different classes of microorganisms. These recognition systems determine microbial location, viability, replication and pathogenicity. Detection of these features by recognition pathways of the innate immune system is translated into different classes of effector responses though specialized populations of dendritic cells. Multiple mechanisms for the induction of immune responses are variations on a common design principle wherein the cells that sense infections produce one set of cytokines to induce lymphocytes to produce another set of cytokines, which in turn activate effector responses. Here we discuss these emerging principles of innate control of adaptive immunity.
Twenty years after the proposal that pattern recognition receptors detect invasion by microbial pathogens, the field of immunology has witnessed several discoveries that have elucidated receptors and ...signaling pathways of microbial recognition systems and how they control the generation of T and B lymphocyte-mediated immune responses. However, there are still many fundamental questions that remain poorly understood, even though sometimes the answers are assumed to be known. Here, we discuss some of these questions, including the mechanisms by which pathogen-specific innate immune recognition activates antigen-specific adaptive immune responses and the roles of different types of innate immune recognition in host defense from infection and injury.
The innate immune system uses multiple strategies to detect viral infections. Because all viruses rely on host cells for their synthesis and propagation, the molecular features used to detect viral ...infections must be unique to viruses and absent from host cells. Research in the past decade has advanced our understanding of various cell-intrinsic and cell-extrinsic modes of virus recognition. This review examines the innate recognition from the point of view of virus invasion and replication strategies, and places innate sensors in the context of detecting viral genome, replication intermediate, transcriptional by-product, and other viral invasion strategies. On the basis of other unique features common to viral infections, undiscovered areas of virus detection are discussed.
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