JP-8 jet fuel exposure suppresses the immune response to viral infections

2008 ◽  
Vol 24 (4) ◽  
pp. 209-216 ◽  
Author(s):  
DT Harris ◽  
D Sakiestewa ◽  
D Titone ◽  
X He ◽  
J Hyde ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Viral Infection ◽  
Viral Infections ◽  
Immune Cell ◽  
Immunosuppressive Agents ◽  
Interleukin 10 ◽  
Jet Fuel ◽  
Us Air Force ◽  
Influenza Viral Infection

The US Air Force has implemented the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Previous work has reported that JP-8 exposure is immunosuppressive. Exposure of mice to JP-8 for 1 h/day resulted in immediate secretion of two immunosuppressive agents, namely, interleukin-10 and prostaglandin E2. Thus, it was of interest to determine if jet fuel exposure might alter the immune response to infectious agents. The Hong Kong influenza model was used for these studies. Mice were exposed to 1000 mg/m3 JP-8 (1 h/day) for 7 days before influenza viral infection. Animals were infected intra-nasally with virus and followed in terms of overall survival as well as immune responses. All surviving animals were killed 14 days after viral infection. In the present study, JP-8 exposure increased the severity of the viral infection by suppressing the anti-viral immune responses. That is, exposure of mice to JP-8 for 1 h/day for 7 days before infection resulted in decreased immune cell viability after exposure and infection, a greater than fourfold decrease in immune proliferative responses to mitogens, as well as an overall loss of CD3+, CD4+, and CD8+ T cells from the lymph nodes, but not the spleens, of infected animals. These changes resulted in decreased survival of the exposed and infected mice, with only 33% of animals surviving as compared with 50% of mice infected but not jet fuel–exposed (and 100% of mice exposed only to JP-8). Thus, short-term, low-concentration JP-8 jet fuel exposures have significant suppressive effects on the immune system which can result in increased severity of viral infections.

scholarly journals Regulation of Antiviral Immune Response by N6-Methyladenosine of mRNA

2021 ◽  
Vol 12 ◽  
Author(s):  
Baoxin Zhao ◽  
Weijie Wang ◽  
Yan Zhao ◽  
Hongxiu Qiao ◽  
Zhiyun Gao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infection ◽  
Viral Infections ◽  
Immune Cell ◽  
Vital Role ◽  
Immune Defense ◽  
Interferon Response ◽  
Adaptive Immune Responses ◽  
Antiviral Immune Response ◽  
Adaptive Immune

Host innate and adaptive immune responses play a vital role in clearing infected viruses. Meanwhile, viruses also evolve a series of mechanisms to weaken the host immune responses and evade immune defense. Recently, N6-methyladenosine (m6A), the most prevalent mRNA modification, has been revealed to regulate multiple steps of RNA metabolism, such as mRNA splicing, localization, stabilization, and translation, thus participating in many biological phenomena, including viral infection. In the process of virus–host interaction, the m6A modification that presents on the virus RNA impedes capture by the pattern recognition receptors, and the m6A modification appearing on the host immune-related molecules regulate interferon response, immune cell differentiation, inflammatory cytokine production, and other immune responses induced by viral infection. This review summarizes the research advances about the regulatory role of m6A modification in the innate and adaptive immune responses during viral infections.

JP-8 jet fuel exposure rapidly induces high levels of IL-10 and PGE2 secretion and is correlated with loss of immune function

2007 ◽  
Vol 23 (4) ◽  
pp. 223-230 ◽  
Author(s):  
David T. Harris ◽  
Debbie Sakiestewa ◽  
Dominic Titone ◽  
Mark Witten
Keyword(s):  
Immune System ◽  
Immune Function ◽  
Immunosuppressive Agents ◽  
Elevated Serum ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Jet Fuel ◽  
Us Air Force ◽  
The Us ◽  
High Level

The US Air Force has implemented the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Previous work has demonstrated that JP-8 exposure is immunosuppressive. In the present study, the potential mechanisms for the effects of JP-8 exposure on the immune system were investigated. Exposure of mice to JP-8 for 1 h/day resulted in immediate secretion of two immunosuppressive agents; namely, interleukin-10 (IL-10) and prostaglandin E2 (PGE2). JP-8 exposure rapidly induced a persistently high level of serum IL-10 and PGE2 at an exposure concentration of 1000 mg/m3. IL-10 levels peaked at 2h post-JP-8 exposure and then stabilized at significantly elevated serum levels, while PGE2 levels peaked after 2—3 days of exposure and then stabilized. Elevated IL-10 and PGE2 levels may at least partially explain the effects of JP-8 exposure on immune function. Elevated IL-10 and PGE2 levels, however, cannot explain all of the effects due to JP-8 exposure (e.g., decreased organ weights and decreased viable immune cells), as treatment with a PGE2 inhibitor did not completely reverse the immunosuppressive effects of jet fuel exposure. Thus, low concentration JP-8 jet fuel exposures have significant effects on the immune system, which can be partially explained by the secretion of immunosuppressive modulators, which are cumulative over time.

scholarly journals Pathogenesis and Immune Response Caused by Vector-Borne and Other Viral Infections in a Tupaia Model

2019 ◽  
Vol 7 (12) ◽  
pp. 686
Author(s):  
Mohammad Enamul Hoque Kayesh ◽  
Md Abul Hashem ◽  
Bouchra Kitab ◽  
Kyoko Tsukiyama-Kohara
Keyword(s):  
Immune Response ◽  
Animal Models ◽  
Immune Responses ◽  
Viral Infection ◽  
Viral Infections ◽  
Tree Shrew ◽  
Clinical Manifestations ◽  
Infection Model ◽  
Host Immune System

The Tupaia or tree shrew (Tupaia belangeri), a small mammal of the Tupaiidae family, is an increasingly used and promising infection model for virological and immunological research. Recently, sequencing of the Tupaia whole genome revealed that it is more homologous to the genome of humans than of rodents. Viral infections are a global threat to human health, and a complex series of events are involved in the interactions between a virus and the host immune system, which play important roles in the activation of an immune response and the outcome of an infection. Majority of immune response data in viral infections are obtained from studies using animal models that enhance the understanding of host-virus interactions; a proper understanding of these interactions is very important for the development of effective antivirals and prophylactics. Therefore, animal models that are permissive to infection and that recapitulate human disease pathogenesis and immune responses to viral infections are essential. Several studies have shown the permissiveness of Tupaia to a number of important human viral infections in vitro and in vivo without prior adaptation of the viruses; the immune responses and clinical manifestations were comparable to those observed in human infections. Thus, the Tupaia is being utilized and developed as a promising immunocompetent small animal model for viral infection studies. In this review, we focused on the immune responses, mostly innate, during viral infection and pathogenesis in the Tupaia model; we evaluated the interaction between the virus and the components of host resistance, the usefulness of this model for immunopathogenesis studies, and the vaccines and antivirals available.

scholarly journals Research progress of siRNA in anti-influenza viral infection

2018 ◽  
Vol 7 (2) ◽  
pp. 50-55
Author(s):  
Li Han
Keyword(s):  
Viral Infection ◽  
Small Interfering Rna ◽  
Viral Infections ◽  
High Specificity ◽  
Research Progress ◽  
Global Pandemic ◽  
New Concepts ◽  
Seasonal Flu ◽  
Influenza Viral Infection ◽  
Interfering Rna

AbstractThe harms of seasonal flu and global pandemic influenza have generally attracted attention. However, the currently administered influenza drugs and flu vaccines have certain limitations. Since the discovery of the small interfering RNA (siRNA) and its mediated RNA interference process, this molecule has been widely used in the study of anti-influenza viral infections because of its high specificity and strong selectivity. The results provided new concepts for the prevention and treatment of influenza virus. However, the siRNA still faces an enormous challenge despite extensive studies on this molecule. The research progress of siRNA in anti-influenza viral infection was reviewed in this study.

scholarly journals A functional spleen contributes to afucosylated IgG in humans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iwona Wojcik ◽  
David E. Schmidt ◽  
Lisa A. de Neef ◽  
Minke A. E. Rab ◽  
Bob Meek ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Immune Cell ◽  
Lymphoid Organ ◽  
Immune Effector ◽  
Adaptive Immune ◽  
Wide Range ◽  
Humoral Responses ◽  
First Time

AbstractAs a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography–mass spectrometry (LC–MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells.

scholarly journals Mast Cell Responses to Viruses and Pathogen Products

2019 ◽  
Vol 20 (17) ◽  
pp. 4241 ◽  
Author(s):  
Jean S. Marshall ◽  
Liliana Portales-Cervantes ◽  
Edwin Leong
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immune Responses ◽  
Viral Infection ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Local Source ◽  
Type I ◽  
Viral Challenge ◽  
Cell Responses

Mast cells are well accepted as important sentinel cells for host defence against selected pathogens. Their location at mucosal surfaces and ability to mobilize multiple aspects of early immune responses makes them critical contributors to effective immunity in several experimental settings. However, the interactions of mast cells with viruses and pathogen products are complex and can have both detrimental and positive impacts. There is substantial evidence for mast cell mobilization and activation of effector cells and mobilization of dendritic cells following viral challenge. These cells are a major and under-appreciated local source of type I and III interferons following viral challenge. However, mast cells have also been implicated in inappropriate inflammatory responses, long term fibrosis, and vascular leakage associated with viral infections. Progress in combating infection and boosting effective immunity requires a better understanding of mast cell responses to viral infection and the pathogen products and receptors we can employ to modify such responses. In this review, we outline some of the key known responses of mast cells to viral infection and their major responses to pathogen products. We have placed an emphasis on data obtained from human mast cells and aim to provide a framework for considering the complex interactions between mast cells and pathogens with a view to exploiting this knowledge therapeutically. Long-lived resident mast cells and their responses to viruses and pathogen products provide excellent opportunities to modify local immune responses that remain to be fully exploited in cancer immunotherapy, vaccination, and treatment of infectious diseases.

scholarly journals The Mycobacterium tuberculosis Recombinant 27-Kilodalton Lipoprotein Induces a Strong Th1-Type Immune Response Deleterious to Protection

2003 ◽  
Vol 71 (6) ◽  
pp. 3146-3154 ◽  
Author(s):  
Avi-Hai Hovav ◽  
Jacob Mullerad ◽  
Liuba Davidovitch ◽  
Yolanta Fishman ◽  
Fabiana Bigi ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Interleukin 10 ◽  
Control Groups ◽  
Cellular Immune Responses ◽  
Protective Antigens ◽  
Proliferation Response ◽  
Cellular Immune ◽  
Mycobacterial Antigens

ABSTRACT Th1 immune response is essential in the protection against mycobacterial intracellular pathogens. Lipoproteins trigger both humoral and cellular immune responses and may be candidate protective antigens. We studied in BALB/c mice the immunogenicity and the protection offered by the recombinant 27-kDa Mycobacterium tuberculosis lipoprotein and the corresponding DNA vaccine. Immunization with the 27-kDa antigen resulted in high titers of immunoglobulin G1 (IgG1) and IgG2a with a typical Th1 profile and a strong delayed hypersensitivity response. A strong proliferation response was observed in splenocytes, and significant nitric oxide production and gamma interferon secretion but not interleukin 10 secretion were measured. Based on these criteria, the 27-kDa antigen induced a typical Th1-type immune response thought to be necessary for protection. Surprisingly, in 27-kDa-vaccinated mice (protein or DNA vaccines) challenged by M. tuberculosis H37Rv or BCG strains, there was a significant increase in the numbers of CFU in the spleen compared to that for control groups. Furthermore, the protection provided by BCG or other mycobacterial antigens was completely abolished once the 27-kDa antigen was added to the vaccine preparations. This study indicates that the 27-kDa antigen has an adverse effect on the protection afforded by recognized vaccines. We are currently studying how the 27-kDa antigen modulates the mouse immune response.

scholarly journals Immune response profiling of patients with spondyloarthritis reveals signalling networks mediating TNF-blocker function in vivo

2020 ◽  
pp. annrheumdis-2020-218304
Author(s):  
Silvia Menegatti ◽  
Vincent Guillemot ◽  
Eleonora Latis ◽  
Hanane Yahia-Cherbal ◽  
Daniela Mittermüller ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Immune Cell ◽  
Clinical Laboratory ◽  
Prostaglandin E ◽  
Macrophage Polarisation ◽  
Tnf Blockers ◽  
Tnf Blocker ◽  
Therapeutic Responses

ObjectivesAntitumour necrosis factor (TNF) therapy has revolutionised treatment of several chronic inflammatory diseases, including spondyloarthritis (SpA). However, TNF inhibitors (TNFi) are not effective in all patients and the biological basis for treatment failure remains unknown. We have analysed induced immune responses to define the mechanism of action of TNF blockers in SpA and to identify immunological correlates of responsiveness to TNFi.MethodsImmune responses to microbial and pathway-specific stimuli were analysed in peripheral blood samples from 80 patients with axial SpA before and after TNFi treatment, using highly standardised whole-blood stimulation assays. Cytokines and chemokines were measured in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, and gene expression was monitored using nCounter assays.ResultsAnti-TNF therapy induced profound changes in patients’ innate immune responses. TNFi action was selective, and had only minor effects on Th1/Th17 immunity. Modular transcriptional repertoire analysis identified prostaglandin E2 synthesis and signalling, leucocyte recirculation, macrophage polarisation, dectin and interleukin (IL)-1 signalling, as well as the nuclear factor kappa B (NF-kB) transcription factor family as key pathways targeted by TNF blockers in vivo. Analysis of induced immune responses before treatment initiation revealed that expression of molecules associated with leucocyte adhesion and invasion, chemotaxis and IL-1 signalling are correlated with therapeutic responses to anti-TNF.ConclusionsWe show that TNFi target multiple immune cell pathways that cooperate to resolve inflammation. We propose that immune response profiling provides new insight into the biology of TNF-blocker action in patients and can identify signalling pathways associated with therapeutic responses to biological therapies.

GLOBAL PROPERTIES OF A MODEL OF IMMUNE EFFECTOR RESPONSES TO VIRAL INFECTIONS

2007 ◽  
Vol 10 (04) ◽  
pp. 495-503 ◽  
Author(s):  
XIA WANG ◽  
XINYU SONG
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Lyapunov Functions ◽  
Viral Infections ◽  
Reproductive Number ◽  
Asymptotically Stable ◽  
Globally Asymptotically Stable ◽  
Immune Effector ◽  
Global Properties ◽  
Ctl Immune Response

This article proposes a mathematical model which has been used to investigate the importance of lytic and non-lytic immune responses for the control of viral infections. By means of Lyapunov functions, the global properties of the model are obtained. The virus is cleared if the basic reproduction number R0 ≤ 1 and the virus persists in the host if R0 > 1. Furthermore, if R0 > 1 and other conditions hold, the immune-free equilibrium E0 is globally asymptotically stable. The equilibrium E1 exists and is globally asymptotically stale if the CTL immune response reproductive number R1 < 1 and the antibody immune response reproductive number R2 > 1. The equilibrium E2 exists and is globally asymptotically stable if R1 > 1 and R2 < 1. Finally, the endemic equilibrium E3 exists and is globally asymptotically stable if R1 > 1 and R2 > 1.

Ribavirin attenuates the respiratory immune responses to influenza viral infection in mice

2017 ◽  
Vol 162 (6) ◽  
pp. 1661-1669 ◽  
Author(s):  
Shang-hui Liao ◽  
Yun Li ◽  
Yan-ni Lai ◽  
Ni Liu ◽  
Feng-xue Zhang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infection ◽  
Influenza Viral Infection
Sign in / Sign up

Export Citation Format

Share Document