Cytokine expression in the duodenal mucosa of patients with visceral leishmaniasis

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.

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Vaccination and Infection of Swine With Salmonella Typhimurium Induces a Systemic and Local Multifunctional CD4+ T-Cell Response

Frontiers in Immunology ◽

10.3389/fimmu.2020.603089 ◽

2021 ◽

Vol 11 ◽

Author(s):

Selma Schmidt ◽

Elena L. Sassu ◽

Eleni Vatzia ◽

Alix Pierron ◽

Julia Lagler ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

T Cell ◽

Lymph Nodes ◽

T Cell Response ◽

Effector Memory ◽

Cell Immune Response ◽

Control Group ◽

Tnf Α ◽

Ifn Γ

The gram-negative facultative intracellular bacteria Salmonella Typhimurium (STM) often leads to subclinical infections in pigs, but can also cause severe enterocolitis in this species. Due to its high zoonotic potential, the pathogen is likewise dangerous for humans. Vaccination with a live attenuated STM strain (Salmoporc) is regarded as an effective method to control STM infections in affected pig herds. However, information on the cellular immune response of swine against STM is still scarce. In this study, we investigated the T-cell immune response in pigs that were vaccinated twice with Salmoporc followed by a challenge infection with a virulent STM strain. Blood- and organ-derived lymphocytes (spleen, tonsils, jejunal and ileocolic lymph nodes, jejunum, ileum) were stimulated in vitro with heat-inactivated STM. Subsequently, CD4+ T cells present in these cell preparations were analyzed for the production of IFN-γ, TNF-α, and IL-17A by flow cytometry and Boolean gating. Highest frequencies of STM-specific cytokine-producing CD4+ T cells were found in lamina propria lymphocytes of jejunum and ileum. Significant differences of the relative abundance of cytokine-producing phenotypes between control group and vaccinated + infected animals were detected in most organs, but dominated in gut and lymph node-residing CD4+ T cells. IL-17A producing CD4+ T cells dominated in gut and gut-draining lymph nodes, whereas IFN-γ/TNF-α co-producing CD4+ T cells were present in all locations. Additionally, the majority of cytokine-producing CD4+ T cells had a CD8α+CD27- phenotype, indicative of a late effector or effector memory stage of differentiation. In summary, we show that Salmonella-specific multifunctional CD4+ T cells exist in vaccinated and infected pigs, dominate in the gut and most likely contribute to protective immunity against STM in the pig.

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

Cells ◽

10.3390/cells10040868 ◽

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.

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High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection

Life ◽

10.3390/life11060527 ◽

2021 ◽

Vol 11 (6) ◽

pp. 527

Author(s):

Lucero A. Ramon-Luing ◽

Ranferi Ocaña-Guzman ◽

Norma A. Téllez-Navarrete ◽

Mario Preciado-García ◽

Dámaris P. Romero-Rodríguez ◽

...

Keyword(s):

Immune Reconstitution Inflammatory Syndrome ◽

Immune Reconstitution ◽

Control Group ◽

Hiv Patients ◽

Art Initiation ◽

Tnf Α ◽

Ifn Γ ◽

Α Level ◽

Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is an exacerbated immune response that can occur to HIV+ patients after initiating antiretroviral therapy (ART). IRIS pathogenesis is unclear, but dysfunctional and exhausted cells have been reported in IRIS patients, and the TIM-3/Gal-9 axis has been associated with chronic phases of viral infection. This study aimed to evaluate the soluble levels of TIM-3 and Gal-9 and their relationship with IRIS development. TIM-3, Gal-9, TNF-α, IFN-γ, IL-6, TNFR1, TNFR2, E-cadherin, ADAM10, and ADAM17 were measured to search for IRIS-associated biomarkers in plasma samples from 0-, 4-, 8-, 12-, and 24-weeks after ART initiation of 61 HIV+ patients (15 patients developed IRIS, and 46 did not). We found that patients who developed IRIS had higher levels of TIM-3 [median 4806, IQR: 3206–6182] at the time of the IRIS events, compared to any other follow-up time evaluated in these patients or compared with a control group of patients who did not develop IRIS. Similarly, IRIS patients had a higher TNF-α level [median 10.89, IQR: 8.36–12.34] at IRIS events than any other follow-up time evaluated. Other molecules related to the TIM-3 and TNF-α pathway (Gal-9, IL-6, IFN-γ, TNFR1, TNFR2, ADAM-10, and ADAM-17) did not change during the IRIS events. In conclusion, our data suggest that a high level of soluble TIM-3 and TNF-α could be used as an IRIS biomarker.

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

Journal of Virology ◽

10.1128/jvi.76.11.5692-5700.2002 ◽

2002 ◽

Vol 76 (11) ◽

pp. 5692-5700 ◽

Cited By ~ 28

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.

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

Helminthologia ◽

10.1515/helmin-2015-0063 ◽

2016 ◽

Vol 53 (1) ◽

pp. 14-23 ◽

Cited By ~ 2

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.

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Effects of Moringa Oleifera Leaf Polysaccharide on Growth Performance and Immune Response of Broiler Chickens

10.21203/rs.3.rs-1089038/v1 ◽

2021 ◽

Author(s):

Hosameldeen Mohamed Husien ◽

JunJie Huang ◽

WeiLong Peng ◽

ShuMei Zheng ◽

JinGui Li

Keyword(s):

Immune Response ◽

Growth Performance ◽

Broiler Chickens ◽

Moringa Oleifera ◽

The Body ◽

Feed Consumption ◽

Feed Additive ◽

Control Group ◽

High Dose ◽

Tnf Α

Abstract Moringa oleifera (MO) is a widely used as the nutritious and non-traditional feed supplementation containing kinds of bioactive substances. However, the enhancement effect of Moringa oleifera leaf Polysaccharide (MOLP) as a feed additive in broilers growth performance and immunity remains unclear. In this study, MOLP was obtained by water extraction and alcohol precipitation method, then purified with Trichloroacetic acid (TCA) assay. Chickens were randomly divided into 4 groups, to receive different doses of MOLP (0, 0.1, 0.2, 0.4g/kg) in feed for 3 weeks. The body weight gain (BWG) and feed consumption were recorded for feed conversion ratio (FCR) and average daily feed intake (ADFI) calculation. Broiler chickens were sacrificed and sampled on day 14, 21, 28 (D 14, D 21, and D 28) respectively. Serological indicators, including total protein (TP), albumin (ALB), globulin (GLO), and creatinine (CREA) were detected. ELISA kits were applied for detecting the levels of immunoglobulin A (IgA), immunoglobulin G (IgG), interleukin-2 (IL-2), and tumor necrosis factor (TNF-α). From D 21 to D 28, the results showed that middle dose of MOLP significantly increased BWG and ADFI as well as liver and bursa indexes when compared with the control group. In addition, TP and GLO were also increased (P<0.05). All MOLP treatments enhanced the serum concentrations of IgG and IL-2 (P<0.01). Furthermore, results of quantitative RT-PCR showed that high dose of MOLP treatment significantly increased (P<0.001) the mRNA expression levels of IL-2 and TNF-α of chickens relative to the control group. In conclusion, the results showed that MOLP supplementation contributed to improve growth performance and immune response in broiler chickens, and MOLP could be considered as a promising feed additive.

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In situ cytokine gene expression in early stage of virulent Newcastle disease in chickens

Veterinary Pathology ◽

10.1177/03009858211045945 ◽

2021 ◽

pp. 030098582110459

Author(s):

Corrie Brown ◽

Jian Zhang ◽

Mary Pantin-Jackwood ◽

Kiril Dimitrov ◽

Helena Lage Ferreira ◽

...

Keyword(s):

B Cells ◽

Newcastle Disease ◽

Early Stage ◽

Severe Disease ◽

Cytokine Gene Expression ◽

Lymphoid Tissues ◽

Tnf Α ◽

Virulent Newcastle Disease Virus ◽

Ifn Γ

Selected lymphoid and reproductive tissues were examined from groups of 3-week-old chickens and 62-week-old hens that were inoculated choanally and conjunctivally with 106 EID50 of a virulent Newcastle disease virus (NDV) isolate from the California 2018–2020 outbreak, and euthanized at 1, 2, and 3 days postinfection. In the 3-week-old chickens, immunohistochemistry for NDV and for T and B cell lymphocytes, as well as in situ hybridization for IL-1β, IL-6, IFN-γ, and TNF-α revealed extensive expression of IL-1β and IL-6 in lymphoid tissues, often coinciding with NDV antigen. IFN-γ was only expressed infrequently in the same lymphoid tissues, and TNF-α was rarely expressed. T-cell populations initially expanded but by day 3 their numbers were below control levels. B cells underwent a similar expansion but remained elevated in some tissues, notably spleen, cecal tonsils, and cloacal bursa. Cytokine expression in the 62-week-old hens was overall lower than in the 3-week-old birds, and there was more prolonged infiltration of both T and B cells in the older birds. The strong pro-inflammatory cytokine response in young chickens is proposed as the reason for more severe disease.

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

Arquivo Brasileiro de Medicina Veterinária e Zootecnia ◽

10.1590/1678-6392 ◽

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.

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Pro- and Anti-Inflammatory Cytokines in the First Trimester—Comparison of Missed Miscarriage and Normal Pregnancy

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18168538 ◽

2021 ◽

Vol 18 (16) ◽

pp. 8538

Author(s):

Maciej Kwiatek ◽

Tomasz Gęca ◽

Anna Kwaśniewska

Keyword(s):

Immune Response ◽

Inflammatory Cytokines ◽

First Trimester ◽

Normal Pregnancy ◽

Control Group ◽

Study Group ◽

Tnf Α ◽

Cytokine Levels ◽

Anti Inflammatory ◽

Tgf Β1

The advantage in response of Th2 over Th1 is observed in normal pregnancy in peripheral blood. A disturbance of this balance can lead to symptoms of miscarriage and pregnancy loss. The aim of this study was to evaluate the pro- and anti-inflammatory cytokines in sera of women who were diagnosed with missed miscarriage in the first trimester and to compare this systemic immune response to the response in women with normal pregnancy. The study group consisted of 61 patients diagnosed with missed miscarriage. In total, 19 healthy women with uncomplicated first trimester created the control group. Cytokines were determined in the maternal serum by ELISA. The analysis included INF-γ, TNF-α, Il-1β, Il-4, Il-5, Il-6, Il-9, Il-10, Il-13 and TGF-β1. Th1 cytokine levels in the study group reached slightly higher values for INF-γ, Il-1β and slightly lower for IL-6 and TNF-α. In turn, Th2 cytokine levels in the study group were slightly higher (Il-9, Il-13), significantly higher (Il4, p = 0.015; Il-5, p = 0.0003) or showed no differences with the control group (Il-10). Slightly lower concentration involved only TGF-β1. Analysis of the correlation between levels of pro- and anti-inflammatory cytokines resulted in some discrepancies, without showing predominance of a specific immune response. The results did not confirm that women with missed miscarriage had an advantage in any type of immune response in comparison to women with normal pregnancy.

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Polyphenol Effects on Splenic Cytokine Response in Post-Weaning Contactin 1-Overexpressing Transgenic Mice

Molecules ◽

10.3390/molecules24122205 ◽

2019 ◽

Vol 24 (12) ◽

pp. 2205 ◽

Cited By ~ 1

Author(s):

Thea Magrone ◽

Anna Spagnoletta ◽

Antonella Bizzoca ◽

Matteo Antonio Russo ◽

Emilio Jirillo ◽

...

Keyword(s):

Immune Response ◽

Adaptive Immune Response ◽

Immune Development ◽

Adaptive Immune ◽

Tnf Α ◽

Pregnant Mice ◽

Ifn Γ ◽

Delayed Maturation ◽

Red Grape ◽

Necrosis Factor

Background: In mice, postnatal immune development has previously been investigated, and evidence of a delayed maturation of the adaptive immune response has been detected. Methods: In this study, the effects of red grape polyphenol oral administration on the murine immune response were explored using pregnant mice (TAG/F3 transgenic and wild type (wt) mice) as the animal model. The study was performed during pregnancy as well as during lactation until postnatal day 8. Suckling pups from polyphenol-administered dams as well as day 30 post-weaning pups (dietary-administered with polyphenols) were used. Polyphenol effects were evaluated, measuring splenic cytokine secretion. Results: Phorbol myristate acetate-activated splenocytes underwent the highest cytokine production at day 30 in both wt and TAG/F3 mice. In the latter, release of interferon (IFN)-γ and tumor necrosis factor (TNF)-α was found to be higher than in the wt counterpart. In this context, polyphenols exerted modulating activities on day 30 TAG/F3 mice, inducing release of interleukin (IL)-10 in hetero mice while abrogating release of IL-2, IFN-γ, TNF-α, IL-6, and IL-4 in homo and hetero mice. Conclusion: Polyphenols are able to prevent the development of an inflammatory/allergic profile in postnatal TAG/F3 mice.

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