Age-Related Impairment of Innate and Adaptive Immune Responses Following Intranasal Herpes Simplex Infection

Immune function declines with age, leading to an increased vulnerability to respiratory viral infections. The mechanisms by which aging negatively impacts the innate and adaptive immune system leading to enhanced susceptibility to infections remain to be fully elucidated. In the present study, we used a mouse model of intranasal infection with herpes simplex virus type 1 (HSV-1), a virus that can enter the lungs through the nasal route causing pneumonia, a serious health concern in the elderly. Following intranasal inoculation of young (6 weeks), adult (36 weeks), and aged (68 weeks) with HSV-1 (KOS strain) we: (i) compared the local and systemic innate and adaptive immune response to infection; and (ii) correlated the level and type of immune response to protection against HSV-1 infection. Compared to young and adult mice, aged mice displayed: (i) increased basal level activation of epithelial cells with a decreased expression of TLR3; (ii) increased activation of dendritic cells with increased expression of MHC-1, MHC-II and CD80/86; and (iii) decreased production of type-I interferons upon stimulation; (iv) a delay in cytokines and chemokines production in the lungs; and (v) an impairment in function (CD107 and IFN-g production) of HSV-specific CD8+ T cells. These impairment in innate and adaptive immune responses in aged mice following intranasal HSV-1 inoculation was associated with symptomatic herpes infection. The findings suggest an age-related impairment of both innate and adaptive immune responses which may exacerbate herpes infection and disease in the elderly.

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Overexpression of Interleukin-15 Compromises CD4-Dependent Adaptive Immune Responses against Herpes Simplex Virus 2

Journal of Virology ◽

10.1128/jvi.01282-08 ◽

2008 ◽

Vol 83 (2) ◽

pp. 918-926 ◽

Cited By ~ 19

Author(s):

Navkiran Gill ◽

Ali A. Ashkar

Keyword(s):

Immune Response ◽

T Cells ◽

Herpes Simplex ◽

Immune Responses ◽

Adaptive Immune Response ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Interleukin 15 ◽

Simplex Virus ◽

Herpes Simplex Virus 2

ABSTRACT Interleukin-15 (IL-15) is necessary for the development and function of NK/NKT cells and the maintenance of naive and memory CD8+ T cells. In the absence of IL-15, protective innate immunity is not available; however, a functional adaptive immune response against vaginal herpes simplex virus 2 (HSV-2) is generated. Mice overexpressing IL-15 (IL-15tg mice) have higher numbers of NK cells, greater NK-derived gamma interferon, and more CD8+ T cells. Here we examined the consequences of IL-15 overexpression for innate and adaptive immunity against genital HSV-2. Surprisingly, IL-15tg mice immunized against HSV-2 were not protected against genital HSV-2 challenge compared to control immunized mice. IL-15tg mice had a higher frequency of NK cells in the genital mucosa than control mice. However, immunized IL-15tg mice had significantly lower numbers of HSV-2-specific CD4+ T cells than B6 mice. We then confirmed that CD4+ T cells, but not CD8+ T cells, are essential for protection against intravaginal HSV-2 challenge. Since we observed less protection in immunized IL-15tg mice, we then examined if the adaptive immune responses generated in an environment with overexpression of IL-15 could provide protection against HSV-2 in an environment with normal levels of IL-15 expression. We adoptively transferred immunized cells from IL-15tg and B6 mice into naive RAG-1−/− mice and found that the cells from immunized IL-15tg mice were able to provide protection in this IL-15-normal environment. Our data suggest that overexpression of IL-15 results in a reduced CD4+ T cell-mediated adaptive immune response against genital HSV-2.

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Polluted Air Exposure Compromises Corneal Immunity and Exacerbates Inflammation in Acute Herpes Simplex Keratitis

Frontiers in Immunology ◽

10.3389/fimmu.2021.618597 ◽

2021 ◽

Vol 12 ◽

Author(s):

Victor G. Sendra ◽

Julia Tau ◽

Gustavo Zapata ◽

Romina M. Lasagni Vitar ◽

Eduardo Illian ◽

...

Keyword(s):

Air Pollution ◽

Dendritic Cells ◽

Herpes Simplex ◽

Immune Responses ◽

Lymph Nodes ◽

Adaptive Immune Responses ◽

Air Exposure ◽

Adaptive Immune ◽

Herpes Simplex Keratitis ◽

Hsv 1

Air pollution is a serious environmental issue worldwide in developing countries’ megacities, affecting the population’s health, including the ocular surface, by predisposing or exacerbating other ocular diseases. Herpes simplex keratitis (HSK) is caused by the herpes simplex virus type 1 (HSV-1). The primary or recurring infection in the ocular site causes progressive corneal scarring that may result in visual impairment. The present study was designed to study the immunopathological changes of acute HSK under urban polluted air, using the acute HSK model combined with an experimental urban polluted air exposure from Buenos Aires City. We evaluated the corneal clinical outcomes, viral DNA and pro-inflammatory cytokines by RT-PCR and ELISA assays, respectively. Then, we determined the innate and adaptive immune responses in both cornea and local lymph nodes after HSV-1 corneal by immunofluorescence staining and flow cytometry. Our results showed that mice exposed to polluted air develop a severe form of HSK with increased corneal opacity, neovascularization, HSV-1 DNA and production of TNF-α, IL-1β, IFN-γ, and CCL2. A high number of corneal resident immune cells, including activated dendritic cells, was observed in mice exposed to polluted air; with a further significant influx of bone marrow-derived cells including GR1+ cells (neutrophils and inflammatory monocytes), CD11c+ cells (dendritic cells), and CD3+ (T cells) during acute corneal HSK. Moreover, mice exposed to polluted air showed a predominant Th1 type T cell response over Tregs in local lymph nodes during acute HSK with decreased corneal Tregs. These findings provide strong evidence that urban polluted air might trigger a local imbalance of innate and adaptive immune responses that exacerbate HSK severity. Taking this study into account, urban air pollution should be considered a key factor in developing ocular inflammatory diseases.

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Healthy Effects Exerted by Prebiotics, Probiotics, and Symbiotics with Special Reference to their Impact on the Immune System

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000112 ◽

2012 ◽

Vol 82 (3) ◽

pp. 200-208 ◽

Cited By ~ 23

Author(s):

Emilio Jirillo ◽

Felicita Jirillo ◽

Thea Magrone

Keyword(s):

Immune Responses ◽

Tumor Development ◽

The Elderly ◽

Adaptive Immune Responses ◽

Free Living ◽

Beneficial Effects ◽

Adaptive Immune ◽

Inflammatory Conditions ◽

Reduced Frequency ◽

Inflammatory Bowel

Pre-, pro-, and symbiotics are endowed with a broad spectrum of beneficial effects when administered to animals and humans. A series of experimental and clinical studies have clearly demonstrated that prebiotics, probiotics, or their combination are very effective in attenuating chronic inflammatory conditions such as inflammatory bowel disease or obesity. In addition, these natural products are able to prevent or arrest tumor development, acting on the intestinal microbiota as well as potentiating the immune response.Aging is characterized by a dramatic reduction of both innate and adaptive immune responses, the so-called immunosenescence. This leads to an increased incidence of infections, autoimmune diseases, and cancer in the elderly. Pre-, pro-, and symbiotic administration has been shown to ameliorate the immune response in aging. In particular, administration of a symbiotic to free-living elderly was able to potentiate the release of interleukin-8, thus increasing neutrophils in the host, perhaps explaining the reduced frequency of winter infections in the elderly.

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

10.1101/2021.03.10.21253299 ◽

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.

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Adaptive immunity

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0040 ◽

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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Mutations in a Highly Conserved Motif of nsp1β Protein Attenuate the Innate Immune Suppression Function of Porcine Reproductive and Respiratory Syndrome Virus

Journal of Virology ◽

10.1128/jvi.03069-15 ◽

2016 ◽

Vol 90 (7) ◽

pp. 3584-3599 ◽

Cited By ~ 23

Author(s):

Yanhua Li ◽

Duan-Liang Shyu ◽

Pengcheng Shang ◽

Jianfa Bai ◽

Kang Ouyang ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Innate Immune ◽

Respiratory Syndrome Virus ◽

Adaptive Immune Responses ◽

Virus Growth ◽

Conserved Motif ◽

Adaptive Immune ◽

Infected Cells ◽

Growth Ability

ABSTRACTPorcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 1β (nsp1β) is a multifunctional viral protein, which is involved in suppressing the host innate immune response and activating a unique −2/−1 programmed ribosomal frameshifting (PRF) signal for the expression of frameshifting products. In this study, site-directed mutagenesis analysis showed that the R128A or R129A mutation introduced into a highly conserved motif (123GKYLQRRLQ131) reduced the ability of nsp1β to suppress interferon beta (IFN-β) activation and also impaired nsp1β's function as a PRF transactivator. Three recombinant viruses, vR128A, vR129A, and vRR129AA, carrying single or double mutations in the GKYLQRRLQ motif were characterized. In comparison to the wild-type (WT) virus, vR128A and vR129A showed slightly reduced growth abilities, while the vRR129AA mutant had a significantly reduced growth ability in infected cells. Consistent with the attenuated growth phenotypein vitro, pigs infected with nsp1β mutants had lower levels of viremia than did WT virus-infected pigs. Compared to the WT virus in infected cells, all three mutated viruses stimulated high levels of IFN-α expression and exhibited a reduced ability to suppress the mRNA expression of selected interferon-stimulated genes (ISGs). In pigs infected with nsp1β mutants, IFN-α production was increased in the lungs at early time points postinfection, which was correlated with increased innate NK cell function. Furthermore, the augmented innate response was consistent with the increased production of IFN-γ in pigs infected with mutated viruses. These data demonstrate that residues R128 and R129 are critical for nsp1β function and that modifying these key residues in the GKYLQRRLQ motif attenuates virus growth ability and improves the innate and adaptive immune responses in infected animals.IMPORTANCEPRRSV infection induces poor antiviral innate IFN and cytokine responses, which results in weak adaptive immunity. One of the strategies in next-generation vaccine construction is to manipulate viral proteins/genetic elements involved in antagonizing the host immune response. PRRSV nsp1β was identified to be a strong innate immune antagonist. In this study, two basic amino acids, R128 and R129, in a highly conserved GKYLQRRLQ motif were determined to be critical for nsp1β function. Mutations introduced into these two residues attenuated virus growth and improved the innate and adaptive immune responses of infected animals. Technologies developed in this study could be broadly applied to current commercial PRRSV modified live-virus (MLV) vaccines and other candidate vaccines.

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Dual-Wavelength Photosensitive Nano-in-Micro Scaffold Regulates Innate and Adaptive Immune Responses for Osteogenesis

Nano-Micro Letters ◽

10.1007/s40820-020-00540-z ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Qin Zhao ◽

Miusi Shi ◽

Chengcheng Yin ◽

Zifan Zhao ◽

Jinglun Zhang ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Immune Cells ◽

Inflammatory Responses ◽

Macrophage Polarization ◽

T Cell Response ◽

Dual Wavelength ◽

M2 Macrophage ◽

Adaptive Immune Responses ◽

Adaptive Immune

AbstractThe immune response of a biomaterial determines its osteoinductive effect. Although the mechanisms by which some immune cells promote regeneration have been revealed, the biomaterial-induced immune response is a dynamic process involving multiple cells. Currently, it is challenging to accurately regulate the innate and adaptive immune responses to promote osteoinduction in biomaterials. Herein, we investigated the roles of macrophages and dendritic cells (DCs) during the osteoinduction of biphasic calcium phosphate (BCP) scaffolds. We found that osteoinductive BCP directed M2 macrophage polarization and inhibited DC maturation, resulting in low T cell response and efficient osteogenesis. Accordingly, a dual-targeting nano-in-micro scaffold (BCP loaded with gold nanocage, BCP-GNC) was designed to regulate the immune responses of macrophages and DCs. Through a dual-wavelength photosensitive switch, BCP-GNC releases interleukin-4 in the early stage of osteoinduction to target M2 macrophages and then releases dexamethasone in the later stage to target immature DCs, creating a desirable inflammatory environment for osteogenesis. This study demonstrates that biomaterials developed to have specific regulatory capacities for immune cells can be used to control the early inflammatory responses of implanted materials and induce osteogenesis.

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Crosstalk between Dendritic Cells and Immune Modulatory Agents against Sepsis

Genes ◽

10.3390/genes11030323 ◽

2020 ◽

Vol 11 (3) ◽

pp. 323 ◽

Cited By ~ 1

Author(s):

Guoying Wang ◽

Xianghui Li ◽

Lei Zhang ◽

Abualgasim Elgaili Abdalla ◽

Tieshan Teng ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Immune Responses ◽

Critical Role ◽

Innate Immune ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Th2 Responses ◽

Novel Strategy

Dendritic cells (DCs) play a critical role in the immune system which sense pathogens and present their antigens to prime the adaptive immune responses. As the progression of sepsis occurs, DCs are capable of orchestrating the aberrant innate immune response by sustaining the Th1/Th2 responses that are essential for host survival. Hence, an in-depth understanding of the characteristics of DCs would have a beneficial effect in overcoming the obstacle occurring in sepsis. This paper focuses on the role of DCs in the progression of sepsis and we also discuss the reverse sepsis-induced immunosuppression through manipulating the DC function. In addition, we highlight some potent immunotherapies that could be used as a novel strategy in the early treatment of sepsis.

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Innate and Adaptive Immune Responses to Herpes Simplex Virus

Viruses ◽

10.3390/v1030979 ◽

2009 ◽

Vol 1 (3) ◽

pp. 979-1002 ◽

Cited By ~ 66

Author(s):

Tracy Chew ◽

Kathryne Taylor ◽

Karen Mossman

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Immune Responses ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Simplex Virus

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Differential Regulation of the Immune Response in the Spleen and Liver of Mice Infected withLeishmania donovani

Journal of Tropical Medicine ◽

10.1155/2012/639304 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 27

Author(s):

Rashmi Bankoti ◽

Simona Stäger

Keyword(s):

Immune Response ◽

Immune Responses ◽

Host Defense ◽

Defense Mechanisms ◽

Leishmania Donovani ◽

Differential Regulation ◽

Therapeutic Interventions ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Novel Therapeutic

Immunity to pathogens requires generation of effective innate and adaptive immune responses.Leishmania donovanievades these host defense mechanisms to survive and persist in the host. A better understanding and identification of mechanisms thatL. donovaniemploys for its survival is critical for developing novel therapeutic interventions that specifically target the parasite. This paper will highlight some of the mechanisms that the parasite utilizes for its persistence and also discuss how the immune response is regulated.

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