scholarly journals Aging and Interferons: Impacts on Inflammation and Viral Disease Outcomes

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 708
Author(s):  
Emily Feng ◽  
Elizabeth Balint ◽  
Sophie M. Poznanski ◽  
Ali A. Ashkar ◽  
Mark Loeb
Keyword(s):  
Immune Responses ◽  
Viral Infection ◽  
Adaptive Immune Response ◽  
Severe Infection ◽  
Viral Disease ◽  
Type I ◽  
Adaptive Immune ◽  
Disease Outcomes ◽  
Global Pandemic ◽  
Immune Mediated

As highlighted by the COVID-19 global pandemic, elderly individuals comprise the majority of cases of severe viral infection outcomes and death. A combined inability to control viral replication and exacerbated inflammatory immune activation in elderly patients causes irreparable immune-mediated tissue pathology in response to infection. Key to these responses are type I, II, and III interferons (IFNs), which are involved in inducing an antiviral response, as well as controlling and suppressing inflammation and immunopathology. IFNs support monocyte/macrophage-stimulated immune responses that clear infection and promote their immunosuppressive functions that prevent excess inflammation and immune-mediated pathology. The timing and magnitude of IFN responses to infection are critical towards their immunoregulatory functions and ability to prevent immunopathology. Aging is associated with multiple defects in the ability of macrophages and dendritic cells to produce IFNs in response to viral infection, leading to a dysregulation of inflammatory immune responses. Understanding the implications of aging on IFN-regulated inflammation will give critical insights on how to treat and prevent severe infection in vulnerable individuals. In this review, we describe the causes of impaired IFN production in aging, and the evidence to suggest that these impairments impact the regulation of the innate and adaptive immune response to infection, thereby causing disease pathology.

Identification of a Novel Toll-Like Receptor-Independent Immunoadjuvant Pathway That Depends upon Programmed Cell Death.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 775-775
Author(s):  
Kasper Hoebe ◽  
Edith Janssen ◽  
Bruce Beutler
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Immune Responses ◽  
Ultraviolet Light ◽  
Adaptive Immune Response ◽  
Type I ◽  
Toll Like Receptors ◽  
Adjuvant Effect ◽  
Tlr Signaling ◽  
Adaptive Immune

Abstract Molecules of microbial origin, and synthetic derivatives of these molecules, have long been used for their immuno-adjuvant effect, and as the key sensors of microbial infection, Toll-like receptors (TLRs) are thought to be essential for adjuvanticity. To the contrary, we now demonstrate the existence of a robust, TLR-independent pathway for adjuvant effect: one that is actually far stronger than the TLR-dependent pathway. Activation of Toll-like receptors (TLRs) and the subsequent production of cytokines such as type I interferon leads to the maturation of dendritic cells (DCs) with upregulation of MHC molecules and costimulatory molecules such as CD40, CD80 and CD86, allowing for optimal interaction between DCs and T-cells. We have determined that TLR signal transduction is minimally dependent upon two adapter proteins, MyD88 and TRIF. In compound homozygous mutant (DKO) mice that lack functional MyD88 and TRIF, there is complete abrogation of all TLR signaling. Such animals therefore comprise a unique model with which to study TLR-independent immune responses. We have now used DKO mice to determine whether an adaptive immune response can be obtained in the absence of TLR signaling. As expected, adjuvanticity obtained via “classical” microbial adjuvants such as complete Freund’s adjuvant or LPS was completely absent in DKO mice. However, subcutaneous administration of syngeneic murine cells expressing ovalbumin and rendered apoptotic by exposure to ultraviolet light resulted in a strong T-cell response in vivo, with impressive production of interferon-g by CD8+ cells and efficient killing of EL-4 cells that expressed CD8-specific OVA peptides, both in wildtype and DKO mice. Adjuvanticity was observed only in the context of apoptosis, in that living cells, not exposed to ultraviolet light before injection, induced little or no response. Moreover, the mixture of the protein antigen with apoptotic cells was insufficient to induce an adaptive immune response; rather, only cells that expressed the protein prior to induction of apoptosis were stimulatory. These results indicate the existence of a specific, cell death-dependent mechanism for adjuvanticity that is TLR-independent and induced by endogenous molecules. We propose that this new adjuvant pathway is of fundamental importance to immune responses at large. We believe that it is required for initiation of the adaptive immune response witnessed in the context of allograft rejection, graft-versus-host disease, and autoimmune diseases as well.

SLPI and elafin: one glove, many fingers

2005 ◽  
Vol 110 (1) ◽  
pp. 21-35 ◽  
Author(s):  
Steven E. Williams ◽  
Thomas I. Brown ◽  
Ali Roghanian ◽  
Jean-Michel Sallenave
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Type I ◽  
Adaptive Immune ◽  
Pathological Conditions ◽  
Related Proteins

Elafin and SLPI (secretory leucocyte protease inhibitor) have multiple important roles both in normal homoeostasis and at sites of inflammation. These include antiprotease and antimicrobial activity as well as modulation of the response to LPS (lipopolysaccharide) stimulation. Elafin and SLPI are members of larger families of proteins secreted predominantly at mucosal sites, and have been shown to be modulated in multiple pathological conditions. We believe that elafin and SLPI are important molecules in the controlled functioning of the innate immune system, and may have further importance in the integration of this system with the adaptive immune response. Recent interest has focused on the influence of inflamed tissues on the recruitment and phenotypic modulation of cells of the adaptive immune system and, indeed, the local production of elafin and SLPI indicate that they are ideally placed in this regard. Functionally related proteins, such as the defensins and cathelicidins, have been shown to have direct effects upon dendritic cells with potential alteration of their phenotype towards type I or II immune responses. This review addresses the multiple functions of elafin and SLPI in the inflammatory response and discusses further their roles in the development of the adaptive immune response.

scholarly journals Type III Interferons in Viral Infection and Antiviral Immunity

2018 ◽  
Vol 51 (1) ◽  
pp. 173-185 ◽  
Author(s):  
Jian-hua Zhou ◽  
Yi-ning Wang ◽  
Qiu-yan Chang ◽  
Peng Ma ◽  
Yonghao Hu ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Viral Infection ◽  
Biological Activities ◽  
Adaptive Immune Response ◽  
Immune Defense ◽  
Th2 Cells ◽  
Type I ◽  
Antiviral Immune Response ◽  
Type Iii

Interferons (IFNs) can serve as the first line of immune defense against viral infection. The identification of IFN-λs 1, 2, 3 & 4 (termed as type III IFNs) has revealed that the antiviral immune response to viruses contains more components than the type I IFNs that have been known for more than 50 years. IFN-λs are IFN-λ1 (IL-29), IFN-λ2 (IL-28a), IFN-λ3 (IL-28b) and IFN-λ4, which resembles IFN-λ3. IFN-λs have type I-IFN-like immune responses and biological activities, but our knowledge of these novel players in the antiviral response is not well established. In this review, we try to describe the current information on the expression and function of IFN-λs in the innate antiviral immune defense and IFN-λ2’s role in regulating and shaping the adaptive immune response. We suggest that IFN-λs are key antiviral cytokines, directly performing an antiviral immune response at epithelial surfaces in the early stages of viral infection, and that these cytokines also skew the balance of Th1 and Th2 cells to Th1 phenotype. In addition, genetic polymorphisms in IFN-λ genes can impair antiviral immune responses in clinical treatment.

scholarly journals Role of the Innate Immunity Signaling Pathway in the Pathogenesis of Sjögren’s Syndrome

2021 ◽  
Vol 22 (6) ◽  
pp. 3090
Author(s):  
Toshimasa Shimizu ◽  
Hideki Nakamura ◽  
Atsushi Kawakami
Keyword(s):  
Immune Responses ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Innate Immune ◽  
Type I ◽  
Type I Ifn ◽  
Adaptive Immune ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of the salivary and lacrimal glands and extra-glandular lesions. Adaptive immune response including T- and B-cell activation contributes to the development of SS. However, its pathogenesis has not yet been elucidated. In addition, several patients with SS present with the type I interferon (IFN) signature, which is the upregulation of the IFN-stimulated genes induced by type I IFN. Thus, innate immune responses including type I IFN activity are associated with SS pathogenesis. Recent studies have revealed the presence of activation pattern recognition receptors (PRRs) including Toll-like receptors, RNA sensor retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, and inflammasomes in infiltrating and epithelial cells of the salivary glands among patients with SS. In addition, the activation of PRRs via the downstream pathway such as the type I IFN signature and nuclear factor kappa B can directly cause organ inflammation, and it is correlated with the activation of adaptive immune responses. Therefore, this study assessed the role of the innate immune signal pathway in the development of inflammation and immune abnormalities in SS.

scholarly journals Role of Alternative Splicing in Regulating Host Response to Viral Infection

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1720
Author(s):  
Kuo-Chieh Liao ◽  
Mariano A. Garcia-Blanco
Keyword(s):  
Innate Immunity ◽  
Alternative Splicing ◽  
Immune Responses ◽  
Viral Infection ◽  
Rna Splicing ◽  
Type I ◽  
Host Immune Responses ◽  
Transcriptional Regulatory Mechanisms ◽  
Host Virus Interactions

The importance of transcriptional regulation of host genes in innate immunity against viral infection has been widely recognized. More recently, post-transcriptional regulatory mechanisms have gained appreciation as an additional and important layer of regulation to fine-tune host immune responses. Here, we review the functional significance of alternative splicing in innate immune responses to viral infection. We describe how several central components of the Type I and III interferon pathways encode spliced isoforms to regulate IFN activation and function. Additionally, the functional roles of splicing factors and modulators in antiviral immunity are discussed. Lastly, we discuss how cell death pathways are regulated by alternative splicing as well as the potential role of this regulation on host immunity and viral infection. Altogether, these studies highlight the importance of RNA splicing in regulating host–virus interactions and suggest a role in downregulating antiviral innate immunity; this may be critical to prevent pathological inflammation.

scholarly journals Assessment of the pulmonary adaptive immune response to Cladosporium cladosporioides infection using an experimental mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoping Ma ◽  
Jing Hu ◽  
Yan Yu ◽  
Chengdong Wang ◽  
Yu Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Pulmonary Hemorrhage ◽  
Cladosporium Cladosporioides ◽  
Th2 Cells ◽  
Intercellular Adhesion Molecule ◽  
Post Inoculation ◽  
Adaptive Immune ◽  
Systemic Infections

AbstractCladosporium cladosporioides causes asthma and superficial and deep infections, mostly in immunodeficient individuals and animals. This study aimed to investigate whether C. cladosporioides spores can enter the lungs through pulmonary circulation and influence pulmonary immune response. We intravenously injected mice with C. cladosporioides spore suspension and conducted several assays on the lungs. Pulmonary hemorrhage symptoms and congestion were most severe on days 1, 2, and 3 post-inoculation (PI). Extensive inflammatory cell infiltration occurred throughout the period of infection. More spores and hyphae colonizing the lungs were detected on days 1, 2, and 3 PI, and fewer spores and hyphae were observed within 21 d of infection. Numerous macrophages, dendritic cells, and neutrophils were observed on day 5 PI, along with upregulation of CD54, an intercellular adhesion molecule. Th1 and Th2 cells increased after infection; specifically, Th2 cells increased considerably on day 5 PI. These results suggest that days 2 and 5 PI represent the inflammatory peak in the lungs and that the Th2 and Th1 signaling pathways are potentially involved in pulmonary immune responses. In conclusion, the further adaptive immune responses played important roles in establishing effective pulmonary immunity against C. cladosporioides systemic infections based on innate immune responses.

COVID-19 and nutritional deficiency: a review of existing knowledge

2021 ◽  
Vol 42 (1) ◽  
pp. 77-85
Author(s):  
Meghana Muthuvattur Pallath ◽  
Ashok Kumar Ahirwar ◽  
Satyendra Chandra Tripathi ◽  
Priyanka Asia ◽  
Apurva Sakarde ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infection ◽  
Close Contact ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Antibody Affinity ◽  
Global Pandemic ◽  
Underlying Diseases ◽  
Pro Inflammatory Cytokines

Abstract COVID-19 has resulted in an ongoing global pandemic, which spread largely among people who have had close contact with the infected person. The immunopathology of the SARS-CoV-2 virus includes the production of an excess amount of pro-inflammatory cytokines “a cytokine-storm”. The respiratory system (main), cardiovascular system and the gastrointestinal tract are the most affected body systems during viral infection. It has been found that most of the patients who require admission to hospital are elderly or have chronic underlying diseases. Higher cases of malnutrition and co-morbidities like diabetes mellitus and cardiovascular diseases are reported in elderly patients due to which, the immune system weakens and hence, the response to the virus is diminished in magnitude. A deficiency of micronutrients results in impaired immune responses leading to improper secretion of cytokines, alterations in secretory antibody response and antibody affinity which increases susceptibility to viral infection. The deficiency of various micronutrients in COVID-19 patient can be treated by appropriate nutritional supplements, prescribed after evaluating the patients’ nutritional status. Here we aim to highlight the role of a few particular nutrients namely Vitamin D, Vitamin C, Omega-3 fatty acids, Zinc and Magnesium along with the synergistic roles they play in enhancing immunity and thus, maintaining homeostasis.

scholarly journals SARS-CoV-2 Serology Status Detected by Commercialized Platforms Distinguishes Previous Infection and Vaccination Adaptive Immune Responses

2021 ◽  
Author(s):  
Raymond T. Suhandynata ◽  
Nicholas J. Bevins ◽  
Jenny T. Tran ◽  
Deli Huang ◽  
Melissa A. Hoffman ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Adaptive Immune Response ◽  
Antibody Assay ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Previous Infection ◽  
A Cell

AbstractBackgroundThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 110 million individuals and led to 2.5 million deaths worldwide. As more individuals are vaccinated, the clinical performance and utility of SARS-CoV-2 serology platforms needs to be evaluated.MethodsThe ability of four commercial SARS-CoV-2 serology platforms to detect previous infection or vaccination were evaluated using a cohort of 53 SARS-CoV-2 PCR-positive patients, 89 SARS-CoV-2-vaccinated healthcare workers (Pfizer or Moderna), and 127 SARS-CoV-2 negative patients. Serology results were compared to a cell based SARS-CoV-2 pseudovirus (PSV) neutralizing antibodies assay.ResultsThe Roche S-(spike) antibody and Diazyme neutralizing antibodies (NAbs) assays detected adaptive immune response in 100.0% and 90.1% of vaccinated individuals who received two-doses of vaccine (initial and booster), respectively. The Roche N-(nucleocapsid) antibody assay and Diazyme IgG assay did not detect adaptive immune response in vaccinated individuals. The Diazyme Nabs assay correlated with the PSV SARS-CoV-2 ID50 neutralization titers (R2= 0.70), while correlation of the Roche S-antibody assay was weaker (R2= 0.39). Median PSV SARS-CoV-2 ID50 titers more than doubled in vaccinated individuals who received two-doses of the Moderna vaccine (ID50: 597) compared to individuals that received a single dose (ID50: 284).ConclusionsThe Roche S-antibody and Diazyme NAbs assays robustly detected adaptive immune responses in SARS-CoV-2 vaccinated individuals and SARS-CoV-2 infected individuals. The Diazyme NAbs assay strongly correlates with the PSV SARS-CoV-2 NAbs in vaccinated individuals. Understanding the reactivity of commercially available serology platforms is important when distinguishing vaccination response versus natural infection.SummaryThe Roche S (spike protein)-antibody and Diazyme neutralizing-antibodies (NAbs) assays were evaluated for their clinical utility in the detection of SARS-CoV-2 related adaptive immune responses by testing SARS-CoV-2 PCR-confirmed patients, SARS-CoV-2-vaccinated individuals, and SARS-CoV-2-negative individuals. Commercial serology results were compared to results generated using a cell-based SARS-CoV-2 pseudovirus (PSV) NAbs assay and previously validated SARS-CoV-2 commercial serology assays (Roche N (nucleocapsid protein) antibody and Diazyme IgG). We demonstrate that the Roche S-antibody and Diazyme NAbs assays detected adaptive immune response in SARS-CoV-2 vaccinated individuals and the presence of SARS-CoV-2 PSV NAbs. The Roche S-antibody assay had an observed positive percent agreement (PPA) of 100% for individuals who received two doses of the Pfizer or Moderna vaccine. By contrast, the Roche N assay and Diazyme IgG assay did not detect vaccine adaptive immune responses. Our findings also indicate that the Diazyme NAbs assay correlates strongly with the levels of SARS-CoV-2 ID50 neutralization titers using the PSV Nab assay in vaccinated individuals.

scholarly journals NF-κB Family of Transcription Factors: Central Regulators of Innate and Adaptive Immune Functions

2002 ◽  
Vol 15 (3) ◽  
pp. 414-429 ◽  
Author(s):  
Jorge Caamaño ◽  
Christopher A. Hunter
Keyword(s):  
Transcription Factors ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Regulatory Proteins ◽  
Regulatory Function ◽  
Immune Functions ◽  
Critical Elements ◽  
Adaptive Immune ◽  
Host Pathogen Interaction ◽  
Resistance To Infection

SUMMARY Transcription factors of the Rel/NF-κB family are activated in response to signals that lead to cell growth, differentiation, and apoptosis, and these proteins are critical elements involved in the regulation of immune responses. The conservation of this family of transcription factors in many phyla and their association with antimicrobial responses indicate their central role in the regulation of innate immunity. This is illustrated by the association of homologues of NF-κB, and their regulatory proteins, with resistance to infection in insects and plants (M. S. Dushay, B. Asling, and D. Hultmark, Proc. Natl. Acad. Sci. USA 93:10343-10347, 1996; D. Hultmark, Trends Genet. 9:178-183, 1993; J. Ryals et al., Plant Cell 9:425-439, 1997). The aim of this review is to provide a background on the biology of NF-κB and to highlight areas of the innate and adaptive immune response in which these transcription factors have a key regulatory function and to review what is currently known about their roles in resistance to infection, the host-pathogen interaction, and development of human disease.

Adaptive immunity

2020 ◽  
pp. 325-336
Author(s):  
Paul Klenerman
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Adaptive Immunity ◽  
Innate Immune Response ◽  
Molecular Basis ◽  
Adaptive Immune Response ◽  
Antigenic Specificity ◽  
Adaptive Immune Responses ◽  
Research Attention ◽  
Adaptive Immune

The adaptive immune response is distinguished from the innate immune response by two main features: its capacity to respond flexibly to new, previously unencountered antigens (antigenic specificity), and its enhanced capacity to respond to previously encountered antigens (immunological memory). These two features have provided the focus for much research attention, from the time of Jenner, through Pasteur onwards. Historically, innate and adaptive immune responses have often been treated as separate, with the latter being considered more ‘advanced’ because of its flexibility. It is now clear this not the case, and in recent years the molecular basis for these phenomena has become much better understood.

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