scholarly journals Heavy metal intoxication compromises the host cytokine response in Ascaris Suum model infection

2016 ◽  
Vol 53 (1) ◽  
pp. 14-23 ◽  
Author(s):  
E. Dvorožňáková ◽  
M. Dvorožňáková ◽  
J. Šoltys
Keyword(s):  
Heavy Metal ◽  
Immune Response ◽  
Ascaris Suum ◽  
Cytokine Response ◽  
Parasitic Infections ◽  
Tnf Α ◽  
Ifn Γ ◽  
High Level ◽  
Larval Burden ◽  
Heavy Metal Intoxication

SummaryLead (Pb), Cadmium (Cd) and Mercury (Hg) are recognized for their deleterious effect on the environment and immunity where subsequently compromised immune response affects the susceptibility to the potential parasitic infections. This study examined the host cytokine response after heavy metal intoxication (Pb, Cd, and Hg) and subsequent Ascaris suum infection in BALB/c mice. Pb modulated murine immune response towards the Th2 type of response (delineated by IL-5 and IL-10 cytokine production) what was also dominant for the outcome of A. suum infection. Chronic intoxication with Pb caused a more intensive development of the parasite infection. Cd stimulated the Th1 immune response what was associated with increase in IFN-γ production and reduction of larvae present in the liver of intoxicated mice. The larval burden was also low in mice intoxicated with Hg. This was probably not related to the biased Th1/Th2 type of immune response, but rather to the bad host conditions caused by mercury toxicity and high level of pro-cachectic cytokine TNF-α.

scholarly journals Effect of heavy metal intoxication on macrophage metabolic activity of mice infected with Ascaris suum

2014 ◽  
Vol 51 (3) ◽  
pp. 171-180 ◽  
Author(s):  
M. Jalčová ◽  
E. Dvorožňáková
Keyword(s):  
Heavy Metal ◽  
Metabolic Activity ◽  
Ascaris Suum ◽  
Parasitic Infection ◽  
Parasite Burden ◽  
Peritoneal Macrophages ◽  
Oxygen Radical ◽  
O2 Production ◽  
Larval Burden ◽  
Heavy Metal Intoxication

AbstractThe effect of heavy metal intoxication on superoxide anion (O2 −) production and larval burden during experimental Ascaris suum infection was studied. Mice were chronically intoxicated with lead (Pb), cadmium (Cd) or mercury (Hg) and subsequently infected with A. suum. The metabolic activity of peritoneal macrophages in mice intoxicated with Pb was suppressed and subsequent parasitic infection did not change this inhibition. Cd intoxication increased the superoxide production and also stimulated the activity of this oxygen radical after A. suum infection. Intoxication with Hg had a stimulative effect on the macrophage metabolic activity and subsequent A. suum infection moderately reduced this activity. Parasite burden was different depending on a type of heavy metal intoxication. Pb intoxication moderately increased the parasite burden in the liver and lungs of intoxicated mice. In contrast, Cd and Hg intoxication triggered a marked reduction of A. suum larvae in the liver and lungs of intoxicated mice, respectively. Monitored heavy metals differed in their immunomodulatory effect on metabolic activity of macrophages what also altered the intensity of the parasite infection in the hosts.

scholarly journals Antiviral Cytokine Response in Neuroinvasive and Non-Neuroinvasive West Nile Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 342
Author(s):  
Snjezana Zidovec-Lepej ◽  
Tatjana Vilibic-Cavlek ◽  
Ljubo Barbic ◽  
Maja Ilic ◽  
Vladimir Savic ◽  
...  
Keyword(s):  
Immune Response ◽  
West Nile Virus ◽  
Immune Responses ◽  
West Nile Virus Infection ◽  
Cytokine Response ◽  
Serum Samples ◽  
West Nile ◽  
Tnf Α ◽  
Th17 Cytokines ◽  
Ifn Γ

Data on the immune response to West Nile virus (WNV) are limited. We analyzed the antiviral cytokine response in serum and cerebrospinal fluid (CSF) samples of patients with WNV fever and WNV neuroinvasive disease using a multiplex bead-based assay for the simultaneous quantification of 13 human cytokines. The panel included cytokines associated with innate and early pro-inflammatory immune responses (TNF-α/IL-6), Th1 (IL-2/IFN-γ), Th2 (IL-4/IL-5/IL-9/IL-13), Th17 immune response (IL-17A/IL-17F/IL-21/IL-22) and the key anti-inflammatory cytokine IL-10. Elevated levels of IFN-γ were detected in 71.7% of CSF and 22.7% of serum samples (p = 0.003). Expression of IL-2/IL-4/TNF-α and Th1 17 cytokines (IL-17A/IL-17F/IL-21) was detected in the serum but not in the CSF (except one positive CSF sample for IL-17F/IL-4). While IL-6 levels were markedly higher in the CSF compared to serum (CSF median 2036.71, IQR 213.82–6190.50; serum median 24.48, IQR 11.93–49.81; p < 0.001), no difference in the IL-13/IL-9/IL-10/IFN-γ/IL-22 levels in serum/CSF was found. In conclusion, increased concentrations of the key cytokines associated with innate and early acute phase responses (IL-6) and Th1 type immune responses (IFN-γ) were found in the CNS of patients with WNV infection. In contrast, expression of the key T-cell growth factor IL-2, Th17 cytokines, a Th2 cytokine IL-4 and the proinflammatory cytokine TNF-α appear to be concentrated mainly in the periphery.

scholarly journals Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Fabiana Albani Zambuzi ◽  
Priscilla Mariane Cardoso-Silva ◽  
Ricardo Cardoso Castro ◽  
Caroline Fontanari ◽  
Flavio da Silva Emery ◽  
...  
Keyword(s):  
Immune Response ◽  
Hematological Malignancies ◽  
M2 Macrophage ◽  
M2 Polarization ◽  
Tnf Α ◽  
Monocytes And Macrophages ◽  
Ifn Γ ◽  
And Function ◽  
The Impact

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.

scholarly journals CCL19 enhances CD8+ T-cell responses and accelerates HBV clearance

2021 ◽  
Author(s):  
Yan Yan ◽  
Wei Zhao ◽  
Wei Liu ◽  
Yan Li ◽  
Xu Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Crucial Role ◽  
Cell Activation ◽  
Hbv Infection ◽  
Host Immune System ◽  
Tnf Α ◽  
Ifn Γ ◽  
High Level

Abstract Background Chemokine (C–C motif) ligand 19 (CCL19) is a leukocyte chemoattractant that plays a crucial role in cell trafficking and leukocyte activation. Dysfunctional CD8+ T cells play a crucial role in persistent HBV infection. However, whether HBV can be cleared by CCL19-activated immunity remains unclear. Methods We assessed the effects of CCL19 on the activation of PBMCs in patients with HBV infection. We also examined how CCL19 influences HBV clearance and modulates HBV-responsive T cells in a mouse model of chronic hepatitis B (CHB). In addition, C–C chemokine-receptor type 7 (CCR7) knockdown mice were used to elucidate the underlying mechanism of CCL19/CCR7 axis-induced immune activation. Results From in vitro experiments, we found that CCL19 enhanced the frequencies of Ag-responsive IFN-γ+ CD8+ T cells from patients by approximately twofold, while CCR7 knockdown (LV-shCCR7) and LY294002 partially suppressed IFN-γ secretion. In mice, CCL19 overexpression led to rapid clearance of intrahepatic HBV likely through increased intrahepatic CD8+ T-cell proportion, decreased frequency of PD-1+ CD8+ T cells in blood and compromised suppression of hepatic APCs, with lymphocytes producing a significantly high level of Ag-responsive TNF-α and IFN-γ from CD8+ T cells. In both CCL19 over expressing and CCR7 knockdown (AAV-shCCR7) CHB mice, the frequency of CD8+ T-cell activation-induced cell death (AICD) increased, and a high level of Ag-responsive TNF-α and low levels of CD8+ regulatory T (Treg) cells were observed. Conclusions Findings in this study provide insights into how CCL19/CCR7 axis modulates the host immune system, which may promote the development of immunotherapeutic strategies for HBV treatment by overcoming T-cell tolerance.

scholarly journals Hepatic DR5 Induces Apoptosis and Limits Adenovirus Gene Therapy Product Expression in the Liver

2002 ◽  
Vol 76 (11) ◽  
pp. 5692-5700 ◽  
Author(s):  
Huang-Ge Zhang ◽  
Jinfu Xie ◽  
Liang Xu ◽  
Pingar Yang ◽  
Xin Xu ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Immune Response ◽  
Transgene Expression ◽  
Cell Activation ◽  
Nk Cell ◽  
Death Domain ◽  
Activated T Cells ◽  
Tnf Α ◽  
Product Expression ◽  
Ifn Γ

ABSTRACT A major limitation of adenovirus (Ad) gene therapy product expression in the liver is subsequent elimination of the hepatocytes expressing the gene therapy product. This elimination is caused by both necrosis and apoptosis related to the innate and cell-mediated immune response to the Ad. Apoptosis of hepatocytes can be induced by the innate immune response by signaling through death domain receptors on hepatocytes including the tumor necrosis factor alpha (TNF-α) receptor (TNFR), Fas, and death domain receptors DR4 and DR5. We have previously shown that blocking signaling through TNFR enhances and prolongs gene therapy product expression in the liver. In the present study, we constructed an Ad that produces a soluble DR5-Fc (AdsDR5), which is capable of neutralizing TNF-related apoptosis-inducing ligand (TRAIL). AdsDR5 prevents TRAIL-mediated apoptosis of CD3-activated T cells and decreases hepatocyte apoptosis after AdCMVLacZ administration and enhances the level and duration of lacZ transgene expression in the liver. In addition to blocking TRAIL and directly inhibiting apoptosis, AdsDR5 decreases production of gamma interferon (IFN-γ) and TNF-α and decreases NK cell activation, all of which limit Ad-mediated transgene expression in the liver. These results indicate that (i) AdsDR5 produces a DR5-Fc capable of neutralizing TRAIL, (ii) AdsDR5 can reduce activation of NK cells and reduce induction of IFN-γ and TNF-α after Ad administration, and (iii) administration of AdsDR5 can enhance Ad gene therapy in the liver.

scholarly journals Cytokine expression in the duodenal mucosa of patients with visceral leishmaniasis

2010 ◽  
Vol 43 (4) ◽  
pp. 393-395 ◽  
Author(s):  
Kleber Giovanni Luz ◽  
Felipe Francisco Tuon ◽  
Maria Irma Seixas Duarte ◽  
Guilherme Mariz Maia ◽  
Paulo Matos ◽  
...  
Keyword(s):  
Immune Response ◽  
Gastrointestinal Tract ◽  
Visceral Leishmaniasis ◽  
Intestinal Bacteria ◽  
Duodenal Mucosa ◽  
Control Group ◽  
Tnf Α ◽  
Organ Specific ◽  
Ifn Γ

INTRODUCTION: Visceral leishmaniasis (VL) is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL. METHODS: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-γ, TNF-α and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed. RESULTS: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p < 0.05). No differences in the expression of CD8, TNF-α, IL-10 or IL-4 were demonstrated. The number of cells expressing IFN-γ was lower in the VL patients (p < 0.05). CONCLUSIONS: Low levels of cytokines were found in the gastrointestinal tract of patients with VL. This pattern was not found in other organs affected by the disease. Immunotolerance of this tissue against Leishmania could explain these findings, as occurs with intestinal bacteria.

scholarly journals Profile of IL-2, IL-4, IL-10, IFN- ? , TNF- ? and KC-like cytokines in pregnant bitches

2014 ◽  
Vol 66 (4) ◽  
pp. 1067-1072
Author(s):  
M.A.R. Feliciano ◽  
A.S.L. Silva ◽  
R.M. Crivelaro ◽  
M.E.F. Oliveira ◽  
L.N. Coutinho ◽  
...  
Keyword(s):  
Immune Response ◽  
Natural Killer ◽  
Serum Levels ◽  
Blood Samples ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pathological Pregnancy ◽  
English Bulldog

The aim of this study was to determine the profile of IL-2, IL-4, IL-10, IFN-γ, and TNF-α cytokines and KC-like cells (natural killer) in pregnant bitches, unpublished values for the species. A total of 27 females of the Shi Tzu, Pug, English Bulldog and French breeds, weighing 4-20kg and aged 4-6 years were used. Blood samples were collected from bitches during the anestrous and on the 2nd, 5th, 6th, 7th and 8th week of pregnancy. Serum levels of cytokines were measured by panel MILLIPLEX MAP (CCYTO-90K, MILLIPORE, Billerica, Massachusetts, USA) validated for dogs. Twenty four females showed physiological pregnancy and three bitches showed pathological pregnancy. There was no difference between cytokine values during anestrous and gestational weeks of bitches (P>0.05). However, it was possible to verify the physiological behavior of serum levels during modulation of immune response in the gestational process of animals. In animals with gestational disorders, abnormal values for IL-2, IL-4 and INF-y were noted. It was concluded that serum levels of cytokines evaluated in pregnant bitches can help the better understanding of physiological and pathological gestational processes and correlated immunology in this species.

scholarly journals Laboratory findings in SARS-CoV-2 infections: State of the art

2020 ◽  
Vol 66 (8) ◽  
pp. 1152-1156 ◽  
Author(s):  
Miguel Augusto Martins Pereira ◽  
Isabella Carolina de Almeida Barros ◽  
Ana Luiza Veríssimo Jacob ◽  
Mayara Lopes de Assis ◽  
Salim Kanaan ◽  
...  
Keyword(s):  
State Of The Art ◽  
Case Definitions ◽  
Laboratory Findings ◽  
Laboratory Markers ◽  
Tnf Α ◽  
The Subject ◽  
Ifn Γ ◽  
High Level ◽  
Laboratory Changes ◽  
Worse Prognosis

SUMMARY OBJECTIVE The scientific community is constantly assessing the clinical and laboratory manifestations of COVID-19 in the organism. In view of the fragmentation of the large amount of information, knowledge gaps in relation to laboratory markers, and scarcity of papers in Portuguese, we propose a Literature review on laboratory changes observed in patients infected with SARS-CoV-2. METHODS Analysis of articles published between December 2019 and May 2020 on the PubMed and SciELO databases. The articles were identified, filtered, and evaluated based on the approach to the subject, language, and impact. Then, the articles were subjected to a thorough reading, in full, by 4 (four) independent researchers. RESULTS Leukopenia and lymphopenia were included in most studies, even in case definitions. Platelet count and platelet-lymphocyte ratio, at peak platelet, were associated with advanced age and longer hospital stay. Eosinopenia showed a sensitivity of 74.7% and specificity of 68.7% and, together with increased CRP, these are one of the future prospects for screening for disease. A high level of procalcitonin may indicate bacterial co-infection, leading to a worse prognosis. COVID-19 manifests itself with increased levels of many inflammatory markers such as IL-1, IL-2, IL-6, IL-7, IL-12, IP10, IFN-γ, MIP1A, MCP1, GSCF, TNF-α, and MCP1/CCL2, as well as LDH, ESR, D-dimer, CK, ALT, and AST. CONCLUSION There is a need for further studies on the new SARS-CoV-2. So far, there is no consensus regarding laboratory findings and their usefulness, whether as a prognostic marker, mortality, or disease severity.

scholarly journals SEROPOSITIVITY FOR ASCARIOSIS AND TOXOCARIOSIS AND CYTOKINE EXPRESSION AMONG THE INDIGENOUS PEOPLE IN THE VENEZUELAN DELTA REGION

2015 ◽  
Vol 57 (1) ◽  
pp. 47-55 ◽  
Author(s):  
Zaida Araujo ◽  
Sietze Brandes ◽  
Elena Pinelli ◽  
María A. Bochichio ◽  
Andrea Palacios ◽  
...  
Keyword(s):  
Indigenous Population ◽  
Intestinal Parasites ◽  
Ascaris Suum ◽  
Toxocara Canis ◽  
Hymenolepis Nana ◽  
Blastocystis Hominis ◽  
Tnf Α ◽  
Blotting Technique ◽  
Adults And Children ◽  
Ifn Γ

The present study aimed at measuring seropositivities for infection by Ascaris suum and Toxocara canis using the excretory/secretory (E/S) antigens from Ascaris suum (AES) and Toxocara canis (TES) within an indigenous population. In addition, quantification of cytokine expressions in peripheral blood cells was determined. A total of 50 Warao indigenous were included; of which 43 were adults and seven children. In adults, 44.1% were seropositive for both parasites; whereas children had only seropositivity to one or the other helminth. For ascariosis, the percentage of AES seropositivity in adults and children was high; 23.3% and 57.1%, respectively. While that for toxocariosis, the percentage of TES seropositivity in adults and children was low; 9.3% and 14.3%, respectively. The percentage of seronegativity was comparable for AES and TES antigens in adults (27.9%) and children (28.6%). When positive sera were analyzed by Western blotting technique using AES antigens; three bands of 97.2, 193.6 and 200.2 kDas were mostly recognized. When the TES antigens were used, nine major bands were mostly identified; 47.4, 52.2, 84.9, 98.2, 119.1, 131.3, 175.6, 184.4 and 193.6 kDas. Stool examinations showed that Blastocystis hominis, Hymenolepis nana and Entamoeba coli were the most commonly observed intestinal parasites. Quantification of cytokines IFN-γ, IL-2, IL-6, TGF-β, TNF-α, IL-10 and IL-4 expressions showed that there was only a significant increased expression of IL-4 in indigenous with TES seropositivity (p < 0.002). Ascaris and Toxocara seropositivity was prevalent among Warao indigenous.

scholarly journals The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Mathieu Blot ◽  
◽  
Jean-Baptiste Bour ◽  
Jean Pierre Quenot ◽  
Abderrahmane Bourredjem ◽  
...  
Keyword(s):  
Immune Response ◽  
Mechanical Ventilation ◽  
T Cell ◽  
Immune Modulation ◽  
Plasma Concentrations ◽  
Principal Component ◽  
Cytokine Response ◽  
Cell Phenotype ◽  
Gm Csf ◽  
Tnf Α

Abstract Background Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis. Methods Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared. Results At similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (15 [7–22] vs. 4 (0–15) days; p = 0.0049). COVID-19 patients had lower levels of most classical inflammatory cytokines (G-CSF, CCL20, IL-1β, IL-2, IL-6, IL-8, IL-15, TNF-α, TGF-β), but higher plasma concentrations of CXCL10, GM-CSF and CCL5, compared to non-COVID-19 patients. COVID-19 patients displayed similar T-cell exhaustion to non-COVID-19 patients, but with a more unbalanced inflammatory/anti-inflammatory cytokine response (IL-6/IL-10 and TNF-α/IL-10 ratios). Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariate regression analysis confirmed that GM-CSF, CXCL10 and IL-10 levels were independently associated with the duration of mechanical ventilation. Conclusion We identified a unique cytokine response, with higher plasma GM-CSF and CXCL10 in COVID-19 patients that were independently associated with the longer duration of mechanical ventilation. These cytokines could represent the dysregulated immune response in severe COVID-19, as well as promising therapeutic targets. ClinicalTrials.gov: NCT03505281.

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