Peter Van der Ley, Virgil Ejc Schijns
Delivery of vaccines via the mucosal route is regarded as the most effective mode of immunization to counteract infectious diseases that enter via mucosal tissues, including oral, nasal, pulmonary, intestinal, and urogenital surfaces. Mucosal vaccines not only induce local immune effector elements, such as secretory Immunoglobulin A (IgA) reaching the luminal site of the mucosa, but also systemic immunity. Moreover, mucosal vaccines may trigger immunity in distant mucosal tissues because of the homing of primed antigen-specific immune cells toward local and distant mucosal tissue via the common mucosal immune system...
October 2023: Current Opinion in Immunology
Moïse de Lavergne, Lucie Maisonneuve, Katrina Podsypanina, Bénédicte Manoury
Intracellular Toll-like receptors (TLRs) are key components of the innate immune system. Their expression in antigen-presenting cells (APCs), and in particular dendritic cells (DCs), makes them critical in the induction of the adaptive immune response. In DCs, they interact with the chaperone UNC93B1 that mediates their trafficking from the endoplasmic reticulum (ER) to endosomes where they are cleaved by proteases and activated. All these different steps are also shared by major histocompatibility complex class-II (MHCII) molecules...
October 2023: Current Opinion in Immunology
Molly R Braun, Becca A Flitter, William Sun, Sean N Tucker
Oral vaccines have a distinctive advantage of stimulating immune responses in the mucosa, where numerous pathogens gain entry and cause disease. Although various efforts have been attempted to create recombinant mucosal vaccines that provoke strong immunogenicity, the outcomes in clinical trials have been weak or inconsistent. Therefore, next-generation mucosal vaccines are needed that are more immunogenic. Here, we discuss oral vaccines with an emphasis on a next-generation mucosal vaccine that utilizes a nonreplicating human recombinant adenovirus type-5 (rAd5) vector...
October 2023: Current Opinion in Immunology
Yolanda Rivera-Cuevas, Barbara Clough, Eva-Maria Frickel
Cell-intrinsic defense is an essential part of the immune response against intracellular pathogens regulated by cytokine-induced proteins and pathways. One of the most upregulated families of proteins in this defense system are the guanylate-binding proteins (GBPs), large GTPases of the dynamin family, induced in response to interferon gamma. Human GBPs (hGBPs) exert their antimicrobial activity through detection of pathogen-associated molecular patterns and/or damage-associated molecular patterns to execute control mechanisms directed at the pathogen itself as well as the vacuolar compartments in which it resides...
October 2023: Current Opinion in Immunology
João Mello-Vieira, Tobias Bopp, Ivan Dikic
Cell-autonomous immunity is the first line of defense by which cells recognize and contribute to eliminating invasive pathogens. It is composed of immune signaling networks that sense microbial pathogens, promote pathogen restriction, and stimulate their elimination, including host cell death. Ubiquitination is a pivotal orchestrator of these pathways, by changing the activity of signal transducers and effector proteins in an efficient way. In this review, we will focus on how ubiquitin connects the pathways that sense pathogens to the cellular responses to invaders and shed light on how ubiquitination impacts the microenvironment around the infected cell, stimulating the appropriate immune response...
October 2023: Current Opinion in Immunology
Trung Hm Pham, Denise M Monack
Macrophages function as tissue-immune sentinels and mediate key antimicrobial responses against bacterial pathogens. Yet, they can also act as a cellular niche for intracellular bacteria, such as Salmonella enterica, to persist in infected tissues. Macrophages exhibit heterogeneous activation or polarization, states that are linked to differential antibacterial responses and bacteria permissiveness. Remarkably, recent studies demonstrate that Salmonella and other intracellular bacteria inject virulence effectors into the cellular cytoplasm to skew the macrophage polarization state and reprogram these immune cells into a permissive niche...
October 2023: Current Opinion in Immunology
Pauline Schmitt, Lisa Borkner, Seyed Davoud Jazayeri, Karen N McCarthy, Kingston Hg Mills
Whooping cough, caused by Bordetella pertussis, is still a major cause of morbidity and mortality worldwide. Current acellular pertussis (aP) vaccines induce potent circulating IgG and prevent severe disease in children/adults and in infants born to vaccinated mothers. However, they do not prevent nasal infection, allowing asymptomatic transmission of B. pertussis. Studies in animal models have demonstrated that, unlike natural infection, immunization with aP vaccines fails to induce secretory immunoglobulin A (IgA) or interleukin-17 (IL-17)-secreting tissue-resident memory CD4 T (TRM ) cells, required for sustained sterilizing immunity in the nasal mucosa...
October 2023: Current Opinion in Immunology
Ameya R Kirtane, Chaoyang Tang, Dylan Freitas, Joshua D Bernstock, Giovanni Traverso
mRNA vaccines have played a critical role in controlling the SARS-CoV-2 pandemic, and are being actively studied for use in other diseases. There is a growing interest in applying mRNA vaccines at mucosal surfaces as it enables access to a unique immune reservoir in a less-invasive manner. However, mucosal surfaces present several barriers to mRNA uptake, including degrading enzymes, mucus, and clearance mechanisms. In this mini-review, we discuss our understanding of the immune response to mucosal mRNA vaccines as it compares to systemic mRNA vaccines...
September 28, 2023: Current Opinion in Immunology
Charles S Pavia, Maria M Plummer
The eradication of polio during the latter half of the 20th century can be considered one of the greatest medical triumphs in history. This achievement can be attributed to the development of vaccines that received the public's almost unwavering acceptance of them, especially by parents who had been waiting/hoping for a medical breakthrough that would ensure that their children would not succumb to the devastating effects of infantile paralysis. Sixty years later, the worldwide population was now confronted with an equally devastating disease - Covid-19 - which by the 2020-2021 time period had reached pandemic levels not seen since the flu outbreak of 1918...
August 29, 2023: Current Opinion in Immunology
Naoya Tatsumi, Yosuke Kumamoto
Conventional dendritic cells (cDCs) are potent antigen-presenting cells that consist of developmentally, phenotypically, and functionally distinct subsets. Following immunization, each subset of cDCs acquires the antigen and presents it to CD4T (CD4+ T (cells)) cells with distinct spatiotemporal kinetics in the secondary lymphoid organs, often causing multiple waves of antigen presentation to CD4T cells. Here, we review the current understanding of the kinetics of antigen presentation by each cDC subset and its functional consequences in priming naive CD4T cells, and discuss its implications in the differentiation of CD4T cells...
August 2023: Current Opinion in Immunology
Theodora Agalioti, Filippo Cortesi, Nicola Gagliani
At mucosal barriers, the T helper 17 (TH 17) cell population plays a fundamental role in controlling tissue homeostasis. The adaptability of this population to a more pro-inflammatory or anti-inflammatory function - that is, their functional plasticity and consequently heterogeneity - primarily depends on the environment. We would like to term this process environmental immune adaptation. Interfering with TH 17 cell adaptation leads to pathological consequences, including development of immune-mediated inflammatory diseases or even cancer...
August 2023: Current Opinion in Immunology
Keyi Wang, Vanessa Espinosa, Amariliz Rivera
The detrimental impact of fungal infections to human health has steadily increased over the past decades. In October of 2022, the World Health Organization published the first ever fungal-pathogen priority list highlighting increased awareness of this problem, and the need for more research in this area. There were four distinct fungal pathogens identified as critical priority groups with Aspergillus fumigatus (Af) being the only mold. Af is a common environmental fungus responsible for over 90% of invasive aspergillosis cases worldwide...
July 29, 2023: Current Opinion in Immunology
Ann-Mari Svennerholm, Anna Lundgren
Enterotoxigenic Escherichia coli (ETEC) is a leading cause of diarrhea in children in developing countries and in travelers. WHO has affirmed ETEC as a priority vaccine target, but there is no licensed ETEC vaccine available yet. We here describe recent, promising developments of different live, inactivated, and subunit ETEC candidate vaccines expressing or containing nontoxic enterotoxin and/or colonization factor antigens with a focus on oral vaccines. Many of the ETEC candidate vaccines have been tested in clinical trials for safety and immunogenicity and some of them also for protective efficacy in field trials or in challenge studies...
July 29, 2023: Current Opinion in Immunology
Mangalakumari Jeyanathan, Sam Afkhami, Alisha Kang, Zhou Xing
Increasing global concerns of pandemic respiratory viruses highlight the importance of developing optimal vaccination strategies that encompass vaccine platform, delivery route, and regimens. The decades-long effort to develop vaccines to combat respiratory infections such as influenza, respiratory syncytial virus, and tuberculosis has met with challenges, including the inability of systemically administered vaccines to induce respiratory mucosal (RM) immunity. In this regard, ample preclinical and available clinical studies have demonstrated the superiority of RM vaccination to induce RM immunity over parenteral route of vaccination...
July 25, 2023: Current Opinion in Immunology
Hadar Ben-Arosh, Roi Avraham
Macrophages are phagocytic cells distributed across tissues that sustain homeostasis by constantly probing their local environment. Upon perturbations, macrophages rewire their energy metabolism to execute their immune programs. Intensive research in the field of immunometabolism highlights cell-intrinsic immunometabolites such as succinate and itaconate as immunomodulatory signals. A role for cell-extrinsic stimuli now emerges with evidence for signals that shape macrophages' metabolism in a tissue-specific manner...
July 18, 2023: Current Opinion in Immunology
Lily M Ellzey, Kristin L Patrick, Robert O Watson
In addition to housing the major energy-producing pathways in cells, mitochondria are active players in innate immune responses. One critical way mitochondria fulfill this role is by releasing damage-associated molecular patterns (mtDAMPs) that are recognized by innate sensors to activate pathways including, but not limited to, cytokine expression, selective autophagy, and cell death. Mitochondrial reactive oxygen species (mtROS) is a multifunctional mtDAMP linked to pro- and antimicrobial immune outcomes...
July 12, 2023: Current Opinion in Immunology
Harrison Sudholz, Rebecca B Delconte, Nicholas D Huntington
Over recent years, the use of immune checkpoint inhibitors (ICI) has progressed to first and second-line treatments in several cancer types, transforming patient outcomes. While these treatments target T cell checkpoints, such as PD-1, LAG3 and CTLA-4, their efficacy can be compromised through adaptive resistance whereby tumors acquire mutations in genes regulating neoantigen presentation by MHC-I [93]. ICI-responsive tumor types such as advanced metastatic melanoma typically have a high mutational burden and immune infiltration; however, most patients still do not benefit from ICI monotherapy for a number of reasons [94]...
July 12, 2023: Current Opinion in Immunology
Katrin D Mayer-Barber
Granulocytes are innate immune effector cells with essential functions in host resistance to bacterial infections. I will discuss emerging evidence that during Mycobacterium tuberculosis infection, counter-intuitively, eosinophils are host-protective while neutrophils are host detrimental. Additionally, I will propose a 'tipping-point' model in which neutrophils are an integral part of a feedforward loop driving tuberculosis disease exacerbation.
July 10, 2023: Current Opinion in Immunology
Eli Olson, Malini Raghavan
Major histocompatibility complex class I (MHC class I) molecules facilitate subcellular immune surveillance by presenting peptides on the cell surface. MHC class I assembly with peptides generally happens in the endoplasmic reticulum (ER). Peptides are processed in the cytosol, transported into the ER, and assembled with MHC class I heavy and light chains. However, as many pathogens reside within multiple subcellular organelles, peptide sampling across non-cytosolic compartments is also important...
June 26, 2023: Current Opinion in Immunology
Joshua D Milner
ERBIN and phosphoglucomutase 3 (PGM3) mutations both lead to rare primary atopic disorders characterized by allergic disease and connective tissue abnormalities, though each disorder has its own rather unique pattern of multisystem presentations. Pathway studies show how ERBIN mutations allow for enhanced TGFb signaling, and prevent STAT3 from negative-regulating TGFb signaling. This likely explains many elements of clinical overlap between disorders of STAT3 and TGFb signaling. The excessive TGFb signaling leading to increased IL-4 receptor expression also provides the rationale for precision-based therapy blocking the IL-4 receptor to treat the atopic disease...
June 25, 2023: Current Opinion in Immunology
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