scholarly journals Nutraceuticals in Viral Infections: An Overview of the Immunomodulating Properties

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2410
Author(s):  
Giorgio Costagliola ◽  
Giulia Nuzzi ◽  
Erika Spada ◽  
Pasquale Comberiati ◽  
Elvira Verduci ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Coenzyme Q ◽  
Antimicrobial Effect ◽  
Common Element ◽  
Viral Pathogens ◽  
Differentiation And Proliferation ◽  
Pro Inflammatory Cytokines

Nutraceuticals, including vitamin D, vitamin A, zinc, lactoferrin, polyphenols coenzyme Q, magnesium, and selenium, are implicated in the modulation of the complex molecular pathways involved in the immune response against viral pathogens. A common element of the activity of nutraceuticals is their ability to enhance the innate immune response against pathogens by acting on the major cellular subsets and inducing the release of pro-inflammatory cytokines and antimicrobial peptides. In some cases, this action is accompanied by a direct antimicrobial effect, as evidenced in the specific case of lactoferrin. Furthermore, nutraceuticals act through complex molecular mechanisms to minimize the damage caused by the activation of the immune system against pathogens, reducing the oxidative damage, influencing the antigen presentation, enhancing the differentiation and proliferation of regulatory T cells, driving the differentiation of lymphocyte subsets, and modulating the production of pro-inflammatory cytokines. In this paper, we review the main molecular mechanisms responsible for the immunomodulatory function of nutraceuticals, focusing on the most relevant aspects for the prevention and treatment of viral infections.

scholarly journals Serum Levels of Pro-inflammatory Cytokines in relationship to outcomes in Children with P. falciparum malaria, in Nnewi-South east Nigeria

1970 ◽  
Vol 42 (2) ◽  
pp. 142-146
Author(s):  
EC Okocha ◽  
NC Ibeh ◽  
EO Ukaejiofor ◽  
JC Ebenebe ◽  
JC Aneke ◽  
...  
Keyword(s):  
Immune Response ◽  
Platelet Count ◽  
Falciparum Malaria ◽  
Inflammatory Cytokines ◽  
Parasite Density ◽  
The Body ◽  
World Health ◽  
Inadequate Response ◽  
Monocyte Count ◽  
Pro Inflammatory Cytokines

Background and Objective: In P. falciparum malaria (PFM) infestation there are marked changes in cytokine production as the body mounts an immune response to it. Hence we set out to study these changes.Methods: A total of 158 cases of PFM among children attending the paediatric unit of our hospital and 56 healthy controls were studied. Children with febrile illness were screened for malaria using 10% Giemsa stained blood smear. Patients with positive smears were recruited; co-infected patients – those infected by another organism in addition to plasmodium specie.- were excluded. Whole blood was collected, some into plain tubes for serum cytokine testing and some into EDTA bottles for complete blood count and parasite density (PD) determination. Controls with asymptomatic parasitaemia were excluded.Results: Using the World Health Organization criteria for defining severe malaria; we identified 15 cases of severe and 143 cases of uncomplicated PFM. Significantly elevated levels of interleukin-1 (IL-1), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) were seen in the uncomplicated and severe forms of PFM. It was observed that the elevated cytokine values correlated with PD (in uncomplicated PFM but not in the severe forms). The difference between PD/absolute monocyte count (AMC) ratio was not significant (p=0.13); while PD/platelet count (PC) and PC/ AMC ratios were significant (p=0.01, and 0.03 respectively) when compared between uncomplicated and severe disease.Conclusion: Our data seems to suggest that subjects with an adequate immune response to the parasite density, in terms of pro-inflammatory cytokine levels, presented with uncomplicated disease; while those who have an inadequate response presented with severe disease. The ratios of (PD/PC) and (PC/AMC), in the positive and negative directions respectively, may be predictors of increased disease severity. These observations may have implications for predicting disease outcome and PFM therapy.Key Words: plasmodium falciparum malaria, pro-inflammatory cytokines, Parasite density/Platelet count ratio, Platelet count/Absolute monocyte

scholarly journals Extracellular vesicles from human cardiovascular progenitors trigger a reparative immune response in infarcted hearts

2020 ◽  
Author(s):  
Bruna Lima Correa ◽  
Nadia El Harane ◽  
Ingrid Gomez ◽  
Hocine Rachid Hocine ◽  
José Vilar ◽  
...  
Keyword(s):  
Immune Response ◽  
Extracellular Vesicles ◽  
Inflammatory Cytokines ◽  
Nk Cell ◽  
Inflammatory Monocytes ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Aims The cardioprotective effects of human induced pluripotent stem cell-derived cardiovascular progenitor cells (CPC) are largely mediated by the paracrine release of extracellular vesicles (EV). We aimed to assess the immunological behaviour of EV-CPC, which is a prerequisite for their clinical translation. Methods and results Flow cytometry demonstrated that EV-CPC expressed very low levels of immune relevant molecules including HLA Class I, CD80, CD274 (PD-L1), and CD275 (ICOS-L); and moderate levels of ligands of the natural killer (NK) cell activating receptor, NKG2D. In mixed lymphocyte reactions, EV-CPC neither induced nor modulated adaptive allogeneic T cell immune responses. They also failed to induce NK cell degranulation, even at high concentrations. These in vitro effects were confirmed in vivo as repeated injections of EV-CPC did not stimulate production of immunoglobulins or affect the interferon (IFN)-γ responses from primed splenocytes. In a mouse model of chronic heart failure, intra-myocardial injections of EV-CPC, 3 weeks after myocardial infarction, decreased both the number of cardiac pro-inflammatory Ly6Chigh monocytes and circulating levels of pro-inflammatory cytokines (IL-1α, TNF-α, and IFN-γ). In a model of acute infarction, direct cardiac injection of EV-CPC 2 days after infarction reduced pro-inflammatory macrophages, Ly6Chigh monocytes, and neutrophils in heart tissue as compared to controls. EV-CPC also reduced levels of pro-inflammatory cytokines IL-1α, IL-2, and IL-6, and increased levels of the anti-inflammatory cytokine IL-10. These effects on human macrophages and monocytes were reproduced in vitro; EV-CPC reduced the number of pro-inflammatory monocytes and M1 macrophages, while increasing the number of anti-inflammatory M2 macrophages. Conclusions EV-CPC do not trigger an immune response either in in vitro human allogeneic models or in immunocompetent animal models. The capacity for orienting the response of monocyte/macrophages towards resolution of inflammation strengthens the clinical attractiveness of EV-CPC as an acellular therapy for cardiac repair.

scholarly journals The immunomodulatory effect of cathelicidin-B1 on chicken macrophages

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Lianci Peng ◽  
Maaike R. Scheenstra ◽  
Roel M. van Harten ◽  
Henk P. Haagsman ◽  
Edwin J. A. Veldhuizen
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Inflammatory Cytokines ◽  
Culture Conditions ◽  
Titration Calorimetry ◽  
Macrophage Response ◽  
Microbial Infections ◽  
Chicken Macrophage ◽  
Inflammatory Profile ◽  
Pro Inflammatory Cytokines

Abstract Cathelicidins (CATHs) play an important role in the innate immune response against microbial infections. Among the four chicken cathelicidins, CATH-B1 is studied the least. In this study, the effect of CATH-B1 on the macrophage response towards avian pathogenic E. coli (APEC) and bacterial ligands was investigated. Our results show that APEC induced CATH-B1 gene expression in both a chicken macrophage cell line (HD11 cells) and primary macrophages, while expression of the other three CATHs was virtually unaffected. While the antimicrobial activity of CATH-B1 is very low under cell culture conditions, it enhanced bacterial phagocytosis by macrophages. Interestingly, CATH-B1 downregulated APEC-induced gene expression of pro-inflammatory cytokines (IFN-β, IL-1β, IL-6 and IL-8) in primary macrophages. In addition, CATH-B1 pre-incubated macrophages showed a significantly higher gene expression of IL-10 after APEC challenge, indicating an overall anti-inflammatory profile for CATH-B1. Using isothermal titration calorimetry (ITC), CATH-B1 was shown to bind LPS. This suggests that CATH-B1 reduces toll like receptor (TLR) 4 dependent activation by APEC which may partly explain the decreased production of pro-inflammatory cytokines by macrophages. On the contrary, direct binding of CATH-B1 to ODN-2006 enhanced the TLR21 dependent activation of macrophages as measured by nitric oxide production. In conclusion, our results show for the first time that CATH-B1 has several immunomodulatory activities and thereby could be an important factor in the chicken immune response.

scholarly journals WNT ligands contribute to the immune response during septic shock and amplify endotoxemia-driven inflammation in mice

2017 ◽  
Vol 1 (16) ◽  
pp. 1274-1286 ◽  
Author(s):  
Marcela Gatica-Andrades ◽  
Dimitrios Vagenas ◽  
Jessica Kling ◽  
Tam T. K. Nguyen ◽  
Helen Benham ◽  
...  
Keyword(s):  
Septic Shock ◽  
Immune Response ◽  
Mouse Model ◽  
Differential Expression ◽  
Inflammatory Cytokines ◽  
Key Points ◽  
Wnt Ligands ◽  
Pro Inflammatory Cytokines

Key Points Differential expression of WNT ligands in patients with septic shock and a mouse model of endotoxemia correlates with inflammatory cytokines. WNT ligands and WNT/β-catenin signaling positively regulate lipopolysaccharide-induced pro-inflammatory cytokines without impairing IL-10.

scholarly journals Escin Increases the Survival Rate of LPS-Induced Septic Mice Through Inhibition of HMGB1 Release from Macrophages

2015 ◽  
Vol 36 (4) ◽  
pp. 1577-1586 ◽  
Author(s):  
Yajun Cheng ◽  
Hongrui Wang ◽  
Min Mao ◽  
Chao Liang ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Survival Rate ◽  
Western Blot ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Post Treatment ◽  
Mrna Levels ◽  
Treatment Methods ◽  
Protein Levels ◽  
Qrt Pcr ◽  
Pro Inflammatory Cytokines

Background: Previous studies have described the effects of Escin on improving the survival rate of endotoxemic animals. The purpose of this study was to explore the molecular mechanisms of this potentially beneficial treatment. Methods: First, the survival rate of endotoxemic mice was monitored for up to 2 weeks after Escin pretreatment, Escin post-treatment, or Escin post-treatment + rHMGB1. The effects of Escin on the release of pro-inflammatory cytokines such as TNF-a, IL-1ß, IL-6 and HMGB1 in the serum of endotoxemic mice and LPS-induced macrophages were evaluated by ELISA. Furthermore, the mRNA and protein levels of HMGB1 in LPS-induced macrophages were measured by qRT-PCR and Western blot, respectively. Additionally, the release of pro-inflammatory cytokines such as TNF-a, IL-1ß, IL-6 was evaluated by ELISA in rHMGB1-induced macrophages. Finally, the protein levels and the activity of NF-κB in macrophages were checked by Western blot and ELISA, respectively. Results: Both pretreatment and post-treatment with Escin could improve the survival rate of endotoxemic mice, while exogenous rHMGB1 reversed this effect. In addition, Escin decreased the level of the pro-inflammatory cytokines TNF-a, IL-1ß, IL-6 and HMGB1 in endotoxemic mice and in LPS-induced macrophages. Escin could also inhibit the mRNA levels and activity of HMGB1. The release of the pro-inflammatory cytokines TNF-a, IL-1ß, IL-6 could be suppressed in rHMGB1-induced macrophages by Escin. Finally, Escin could suppress the activation of NF-κB in LPS-induced macrophages. Conclusion: Escin could improve the survival of mice with LPS-induced endotoxemia. This effect maybe meditated by reducing the release of HMGB1, resulting in the suppression of the release of pro-inflammatory cytokines.

scholarly journals How fragile we are. Influence of STimulator of INterferon Genes, STING, variants on pathogen recognition and immune response efficiency

2021 ◽  
Author(s):  
Jeremy Morere ◽  
Cecilia Hognon ◽  
Tom Miclot ◽  
Tao Jiang ◽  
Elise Dumont ◽  
...  
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Dynamical Behavior ◽  
Structural Features ◽  
Type I Interferons ◽  
Machine Learning Techniques ◽  
Type I ◽  
Interaction Patterns

The STimulator of INterferon Genes (STING) protein is a cornerstone of the human immune response. Its activation by cGAMP upon the presence of cytosolic DNA stimulates the production of type I interferons and inflammatory cytokines which are crucial for protecting cells from infections. STING signaling pathway can also influence both tumor-suppressive and tumor-promoting mechanisms, rendering it an appealing target for drug design. In the human population, several STING variants exist and exhibit dramatic differences in their activity, impacting the efficiency of the host defense against infections. Understanding the differential molecular mechanisms exhibited by these variants is of utmost importance notably towards personalized medicine treatments against diseases such as viral infections (COVID-19, Dengue...), cancers, or auto-inflammatory diseases. Owing to micro-seconds scale molecular modeling simulations and post-processing by contacts analysis and Machine Learning techniques, we reveal the dynamical behavior of four STING variants (wild type, G230A, R293Q, and G230A-R293Q) and we rationalize the variability of efficiency observed experimentally. Our results show that the decrease of STING activity is linked to a stiffening of key-structural features of the binding cavity, together with changes of the interaction patterns within the protein.

scholarly journals Down Regulation Of IL-1β Secretion By Tgf-β1 In Macrophages Infected With Dengue Virus

2021 ◽  
Author(s):  
Brenda Ramírez-Aguero ◽  
Javier Serrato-Salas ◽  
José Luis Montiel-Hernández ◽  
Judith González-Christen
Keyword(s):  
Immune Response ◽  
Dengue Virus ◽  
Inflammatory Cytokines ◽  
Denv Infection ◽  
Inhibitory Effect ◽  
Microvascular Endothelium ◽  
Infected Cells ◽  
Tgf Β1 ◽  
Pro Inflammatory Cytokines

AbstractSeveral pathogenic mechanisms have been linked to the severity of dengue virus infection, like viral cytotoxicity, underlying host genetics and comorbidities such as diabetes and dyslipidemia. It has been observed that patients with severe manifestations develop an uncontrolled immune response, with an increase in pro-inflammatory cytokines such as TNF, IL-1β, IL-8, IL-6 and chemokines that damage the human microvascular endothelium, and also in anti-inflammatory cytokines IL-4, IL-10 and TGF-β1. The role of TGF-β1 on dengue is not clear; few studies have been published, and most of them from patient sera data, with both protective and pathological roles have described. The aim of this study was to evaluate the ability of TGF-β1 to regulate the secretion of IL-1β in macrophages infected by DENV using THP-1 cells treated with recombinant TGF-β1 before or after DENV infection. By RT-PCR we did not observe a difference in IL-1β expression between infected cells pretreated with TGF-β1 and those that were not. However, secretion of IL-1β was reduced only in cells stimulated with TGF-β1 before infection, and not in those treated 2 hours post-infection. TGF-β1 receptor blockage with SB505124 inhibitor, prior to the addition of TGF-β1 and infection, abrogated the inhibitory effect of TGF-β1. Our results suggest that DENV could regulate the function of TGF-β1 on macrophages. This negative regulation of the TGF-β1 pathway could be used by DENV to evade the immune response and could contribute to the immunopathology.

scholarly journals Interaction of bacterial extracellular microvesicles with eukaryotic cells.

2021 ◽  
Vol 22 (6) ◽  
pp. 1065-1084
Author(s):  
D. S. Shlykova ◽  
V. M. Pisarev ◽  
A. M. Gaponov ◽  
A. V. Tutelyan
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Inflammatory Cytokines ◽  
Human Body ◽  
Molecular Mechanisms ◽  
Host Cells ◽  
Eukaryotic Cells ◽  
Signal Molecules ◽  
Opportunistic Bacteria ◽  
Cytokines Secretion

Bacterial extracellular microvesicles (BMV) are formed by nonpathogenic, pathogenic and opportunistic bacteria. BMV are spherical bilayer-membrane organelles containing different cargoes: lipopolysaccharides, pathogen associated molecular patterns (PUMP), DNA, RNA, signal molecules, proteins, antibiotic resistance factors, virulence factors, toxins providing various immune response options and conducive to the survival and pathogen dissemination in the human body. BMVs secretion play an important role in the ability of microorganisms to cause various diseases. BMV are involved in biofilms formation, help bacteria to obtain nutrition in a nutrient-poor conditions, to evade the host's immune response, provide communication and surviving in a stressful environment during infection inside the host. The heterogeneity of the biogenesis mechanisms causes differences in the BMV and their characteristics including virulence rate. BMVs host cells entering is mediated by several mechanisms and helps to activate innate and adaptive immune reactions. This review focuses on interaction study of BMV with various eukaryotic cells types including neutrophils, dendritic cells, macrophages, epithelial, endothelial cells. This interaction depends on bacteria species, type of target cell and number of vesicles and can lead to different responses: non-immunogenic, pro-inflammatory, cytotoxic. Subcellular and molecular mechanisms related to the involvement of extracellular microvesicles in host's immune response modulation are presented. Stimulation of immune response is provided by increased secretion of proinflammatory cytokines and chemokines. In some cases BMV use mechanisms to evade immune surveillance: anti-inflammatory cytokines secretion, alterations of phagocytosis and chemotaxis of macrophages, increasing the proteolytic cleavage of CD14 on the macrophage surface, alterations of antigen-presenting function of dendritic cells, T-cell proliferation suppression, reducing the pro-inflammatory cytokines secretion, evasion of host-immune cells direct interactions, destruction of neutrophilic traps. These features allow bacterial cells to survive in the human body, increase their invasive potential, and reduce the excessive inflammatory reactions leading to death of the pathogen itself and life-threatening damage of tissues and organs of the host. Further studies of these mechanisms will improve existing therapeutic approaches to the infectious diseases treatment.

scholarly journals Primate innate immune responses to bacterial and viral pathogens reveals an evolutionary trade-off between strength and specificity

2021 ◽  
Vol 118 (13) ◽  
pp. e2015855118
Author(s):  
Mohamed B. F. Hawash ◽  
Joaquin Sanz-Remón ◽  
Jean-Christophe Grenier ◽  
Jordan Kohn ◽  
Vania Yotova ◽  
...  
Keyword(s):  
Immune Response ◽  
Genetic Relatedness ◽  
Viral Infections ◽  
Transcriptional Response ◽  
Transcriptional Responses ◽  
Potential Cost ◽  
Viral Pathogens ◽  
Increased Sensitivity ◽  
Bacterial Stimulation ◽  
Interferon Responses

Despite their close genetic relatedness, apes and African and Asian monkeys (AAMs) differ in their susceptibility to severe bacterial and viral infections that are important causes of human disease. Such differences between humans and other primates are thought to be a result, at least in part, of interspecies differences in immune response to infection. However, because of the lack of comparative functional data across species, it remains unclear in what ways the immune systems of humans and other primates differ. Here, we report the whole-genome transcriptomic responses of ape species (human and chimpanzee) and AAMs (rhesus macaque and baboon) to bacterial and viral stimulation. We find stark differences in the responsiveness of these groups, with apes mounting a markedly stronger early transcriptional response to both viral and bacterial stimulation, altering the transcription of ∼40% more genes than AAMs. Additionally, we find that genes involved in the regulation of inflammatory and interferon responses show the most divergent early transcriptional responses across primates and that this divergence is attenuated over time. Finally, we find that relative to AAMs, apes engage a much less specific immune response to different classes of pathogens during the early hours of infection, up-regulating genes typical of anti-viral and anti-bacterial responses regardless of the nature of the stimulus. Overall, these findings suggest apes exhibit increased sensitivity to bacterial and viral immune stimulation, activating a broader array of defense molecules that may be beneficial for early pathogen killing at the potential cost of increased energy expenditure and tissue damage.

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