scholarly journals Chronic ingestion of deoxynivalenol and fumonisin, alone or in interaction, induces morphological and immunological changes in the intestine of piglets

2011 ◽  
Vol 107 (12) ◽  
pp. 1776-1786 ◽  
Author(s):  
Ana-Paula F. L. Bracarense ◽  
Joelma Lucioli ◽  
Bertrand Grenier ◽  
Graziela Drociunas Pacheco ◽  
Wulf-Dieter Moll ◽  
...  
Keyword(s):  
Immune Cells ◽  
Control Diet ◽  
Cytokine Expression ◽  
Rt Pcr ◽  
Histological Changes ◽  
Tnf Α ◽  
Junction Protein ◽  
Chronic Ingestion ◽  
Ifn Γ ◽  
Junction Proteins

Deoxynivalenol (DON) and fumonisins (FB) are mycotoxins produced by Fusarium species, which naturally co-occur in animal diets. The gastrointestinal tract represents the first barrier met by exogenous food/feed compounds. The purpose of the present study was to investigate the effects of DON and FB, alone and in combination, on some intestinal parameters, including morphology, histology, expression of cytokines and junction proteins. A total of twenty-four 5-week-old piglets were randomly assigned to four different groups, receiving separate diets for 5 weeks: a control diet; a diet contaminated with either DON (3 mg/kg) or FB (6 mg/kg); or both toxins. Chronic ingestion of these contaminated diets induced morphological and histological changes, as shown by the atrophy and fusion of villi, the decreased villi height and cell proliferation in the jejunum, and by the reduced number of goblet cells and lymphocytes. At the end of the experiment, the expression levels of several cytokines were measured by RT-PCR and some of them (TNF-α, IL-1β, IFN-γ, IL-6 and IL-10) were significantly up-regulated in the ileum or the jejunum. In addition, the ingestion of contaminated diets reduced the expression of the adherent junction protein E-cadherin and the tight junction protein occludin in the intestine. When animals were fed with a co-contaminated diet (DON+FB), several types of interactions were observed depending on the parameters and segments assessed: synergistic (immune cells); additive (cytokines and junction protein expression); less than additive (histological lesions and cytokine expression); antagonistic (immune cells and cytokine expression). Taken together, the present data provide strong evidence that chronic ingestion of low doses of mycotoxins alters the intestine, and thus may predispose animals to infections by enteric pathogens.

scholarly journals The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering the Immune Responses against Mycobacterium bovis BCG Strain in Individuals with Type 2 Diabetes

2021 ◽  
Vol 12 (1) ◽  
pp. 16-26
Author(s):  
Kimberly To ◽  
Ruoqiong Cao ◽  
Aram Yegiazaryan ◽  
James Owens ◽  
Kayvan Sasaninia ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Immune Cells ◽  
Mycobacterial Infection ◽  
Drug Resistant ◽  
Tnf Α ◽  
Resistant Strains ◽  
Ifn Γ ◽  
Drug Resistant Strains

Abstract Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) still remains a devastating infectious disease in the world. There has been a daunting increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. T2DM patients are three times more vulnerable to M. tb infection compared to healthy individuals. TB-T2DM coincidence is a challenge for global health control. Despite some progress in the research, M. tb still has unexplored characteristics in successfully evading host defenses. The lengthy duration of treatment, the emergence of multi-drug-resistant strains and extensive-drug-resistant strains of M. tb have made TB treatment very challenging. Previously, we have tested the antimycobacterial effects of everolimus within in vitro granulomas generated from immune cells derived from peripheral blood of healthy subjects. However, the effectiveness of everolimus treatment against mycobacterial infection in individuals with T2DM is unknown. Furthermore, the effectiveness of the combination of in vivo glutathione (GSH) supplementation in individuals with T2DM along with in vitro treatment of isolated immune cells with everolimus against mycobacterial infection has never been tested. Therefore, we postulated that liposomal glutathione (L-GSH) and everolimus would offer great hope for developing adjunctive therapy for mycobacterial infection. L-GSH or placebo was administered to T2DM individuals orally for three months. Study subjects’ blood was drawn pre- and post-L-GSH/or placebo supplementation, where Peripheral Blood Mononuclear Cells (PBMCs) were isolated from whole blood to conduct in vitro studies with everolimus. We found that in vitro treatment with everolimus, an mTOR (membrane target of rapamycin) inhibitor, significantly reduced intracellular M. bovis BCG infection alone and in conjunction with L-GSH supplementation. Furthermore, we found L-GSH supplementation coupled with in vitro everolimus treatment produced a greater effect in inhibiting the growth of intracellular Mycobacterium bovis BCG, than with the everolimus treatment alone. We also demonstrated the functions of L-GSH along with in vitro everolimus treatment in modulating the levels of cytokines such as IFN-γ, TNF-α, and IL-2 and IL-6, in favor of improving control of the mycobacterial infection. In summary, in vitro everolimus-treatment alone and in combination with oral L-GSH supplementation for three months in individuals with T2DM, was able to increase the levels of T-helper type 1 (Th1) cytokines IFN-γ, TNF-α, and IL-2 as well as enhance the abilities of granulomas from individuals with T2DM to improve control of a mycobacterial infection.

scholarly journals Augmentation of Cellular Immunity and Reduction of Influenza Virus Titer in Aged Mice Fed Lactobacillus casei Strain Shirota

2002 ◽  
Vol 9 (1) ◽  
pp. 105-108 ◽  
Author(s):  
Tetsuji Hori ◽  
Junko Kiyoshima ◽  
Kan Shida ◽  
Hisako Yasui
Keyword(s):  
Influenza Virus ◽  
Oral Administration ◽  
Cellular Immunity ◽  
Lactobacillus Casei ◽  
Control Diet ◽  
Killer Activity ◽  
Aged Mice ◽  
Tnf Α ◽  
Ifn Γ ◽  
Upper Respiratory

ABSTRACT We investigated whether oral administration of Lactobacillus casei strain Shirota activates the cellular immune system and ameliorates influenza virus (IFV) titer in the nasal site in upper respiratory IFV infection by using aged mice. Natural killer activity of splenocytes and lung cells of aged mice fed an L. casei strain Shirota diet (L.casei strain Shirota group) was significantly (P < 0.01 and P < 0.05) increased compared to those fed a control diet (control group). The increases were 1.5- and 2.5-fold, respectively. In aged mice fed an XL.casei strain Shirota diet, potent induction of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), which play a very important role in excluding IFV, was evident in nasal lymphocytes. IFN-γ and TNF-α production increased 12- and 3.5-fold, respectively. In this model of upper respiratory IFV infection, the titer of IFV in the nasal washings of aged mice fed an L.casei strain Shirota diet was significantly (P < 0.05) lower than that in aged mice fed a control diet (101.6 ± 0.6 and 102.2 ± 0.5, respectively). These findings suggest that oral administration of L.casei strain Shirota activates not only systemic cellular immunity but also local cellular immunity and that it ameliorates IFV infection.

scholarly journals The Immunomodulatory Effect of Triptolide on Mesenchymal Stem Cells in Vitro

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5011-5011
Author(s):  
Haiping He ◽  
Atsuko Takahashi ◽  
Yuki Yamamoto ◽  
Akiko Hori ◽  
Yuta Miharu ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Cd8 T Cells ◽  
Research Funding ◽  
Complete Medium ◽  
Surface Markers ◽  
Rt Pcr ◽  
Tnf Α ◽  
Ifn Γ

Background: Mesenchymal stromal cells (MSC) are known to have the immunosuppressive ability and have been applied in clinic to treat acute graft-versus-host disease (GVHD), as one of severe complications after hematopoietic stem cells transplantation (HSCT) in Japan. However, MSC are activated to suppress the immune system only upon the stimulation of inflammatory cytokines and the clinical results of MSC therapies for acute GVHD are varied. It is ideal that MSC are primed to be activated and ready to suppress the immunity (=priming) before administration in vivo. Triptolide (TPL) is a diterpene triepoxide purified from a Chinese herb - Tripterygium Wilfordii Hook F (TWHF). It has been shown to possess anti-inflammatory and immunosuppressive properties in vitro. In this study, we aim to use TPL as the activator for umbilical cord-derived MSC (UC-MSC) to entry stronger immunosuppressive status. Methods: The proliferation of UC-MSC with TPL at the indicated concentrations for different time of 24, 48, 72, and 96 hours. Cell counting kit-8(CCK-8) was added in the culture medium to detect cell toxicity and the absorbance was measured using microplate reader. Flow cytometry was used to identify the MSC surface markers expression. TPL-primed UC-MSC were once replaced with fresh medium and co-culture with mixed lymphocyte reaction (MLR) consisted with mononuclear cells (MNCs) stained with CFSE and irradiated allogenic dendritic cell line (PMDC05) in RPMI 1640 medium supplemented with 10 % FBS (complete medium). IDO-1, SOD1, and TGF-β gene expression in TPL-primed UC-MSC and UC-MSC induced by 10 ng/ml IFN-γ and/or 15 ng/ml TNF-α were evaluated by RT-PCR. PDL1 and PDL2 expression in TPL-primed UC-MSC and UC-MSC in response to IFN-γ and/or TNF-α were checked by Flowjo. Results: Exposure of TPL for UC-MSC for 72hour at the concentration above 0.1 μM resulted in the cell damage significantly. Therefore, we added TPL in UC-MSC at 0.01μM of TPL for up to 48 hours, then washed thourouphly for the following culture for experiments. To evaluate the influence of TPL on the surface markers of UC-MSC, we cultured UC-MSC for 4 hours in complete medium following culture with 0.01μM of TPL for 20 hours (TPL-primed UC-MSC). TPL-primed UC-MSC revealed positive for CD105, CD73, and CD90, negative for CD45, CD34, CD14 or CD11b, CD79α or CD19 and HLA-DR surface molecules as same as the non-primed UC-MSC. In MLR suppression by UC-MSC, the TPL-primed UC-MSC activity revealed stronger anti-proliferative effect on the CD4+ and CD8+ T cells activated by allogeneic DC than those of non-primed UC-MSC in MLR. Furthermore, the TPL-primed UC-MSC promoted the expression of IDO-1, SOD1 and TGF-β in response to IFN-γ+/-TNF-α by RT-PCR and enhanced the expression of PD-L1 by FACS analysis. Discussion:In this study, we found the TPL-primed UC-MSC showed stronger antiproliferative potency on CD4+ and CD8+ T cells compared with non-primed UC-MSC. TPL-primed UC-MSC promoted the expression of IDO-1, SOD1 and TGF-β stimulated by IFN-γ+/-TNF-α, although TPL alone did not induce these factors. Furthermore, we found that the PD1 ligand (PD-L1) was induced in TPL-primed UC-MSC, likely IFN-γ enhanced the PD-L1 expression, evaluated by flowcytometry. These results suggested that TPL-primed UC-MSC seemed more sensitive to be activated as the immunosuppressant. Here, we firstly report the new function of TPL to induce the upregulation of immunosuppressive effect, although the mechanisms of TPL inhibition to MSC need to be explore. Conclusively, TPL-primed UC-MSC might be applied for the immunosuppressive inducer of MSC. Figure Disclosures He: SASAGAWA Medical Scholarship: Research Funding; IMSUT Joint Research Project: Research Funding. Nagamura:AMED: Research Funding. Tojo:AMED: Research Funding; Torii Pharmaceutical: Research Funding. Nagamura-Inoue:AMED: Research Funding.

Transcription Factor BACH2 Inhibits AP1 Proteins JunB and FosL1 in Umbilical Cord Blood (UCB) CD4+ T-Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1743-1743
Author(s):  
Mathew L. Lesniewski ◽  
Laura R. Fanning ◽  
Margeret Kozik ◽  
Richard P. Weitzel ◽  
Yeal Hegerfeldt ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Transcription Factor ◽  
T Cell ◽  
Cd4 T Cells ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Tnf Α ◽  
Ifn Γ ◽  
Sirna Knockdown

Abstract Introduction: Umbilical cord blood (UCB) CD4+ T-cells have been shown to express significant levels of BACH2 transcription factor protein compared to adult blood (AB) CD4+ T-cells. Previously, NFAT1 siRNA knockdown of UCB T-cells exhibited a significantly higher BACH2 mRNA expression, and IFN-γ, TNF-α. and CTLA-4 mRNA levels were significantly suppressed. BACH2, a member of the b-Zip family, has been shown to act as a heterodimer with the bZip protein MafK, as a transcriptional inhibitor via recruitment of a histone deacetylase class II complex (HDAC II) in differentiating B-cells, and neurons. Due to observed inverse expression of BACH2 and NFAT1 in UCB CD4+ T-cells, we hypothesized that BACH2 may regulate transcription factors known to bind with NFAT1 including AP-1 proteins JunB and FosL1. We tested this by siRNA knockdown of BACH2 in primary UCB-derived CD4+ T-cells. Key developmental transcription factors JUNB, FosL1, NFAT1 and downstream IFN-γ, and TNF-α were mRNA analyzed. Methods: UCB T-cells were purified using autoMACs system (Miltenyi). After overnight culture, T-cells were transfected with BACH2 siRNA (Dharmacon) using Amaxa Nucleofector system (Amaxa Inc). Both siRNA treated and control cells were incubated in media for 18 hours, and then stimulated using anti-CD3/anti-CD28 antibodies (BD BioScience). Aliquots of cells were collected at specified time points post-stimulation for protein and total RNA isolation. The relative change in mRNA levels for BACH2, JUNB, FosL1, IFN-γ, NFAT1, and TNF-α were determined by Lightcycler SybrGreen real time RT-PCR system (Roche). siRNA knockdown of BACH2 protein in transfected UCB T-cells was confirmed by western blot. Results: Real-time RT-PCR of BACH2 siRNA treated UCB CD4+ T-cells stimulated with anti-CD3/CD28 antibodies and analyzed after 6 hrs of stimulation showed a 4 log increase in FosL1 and NFAT1 mRNA, a 3 log increase in JunB mRNA, a 5 log increase in IFN-γ as compared to stimulated control UCB T-cells. TNF-α mRNA was decreased by 5 logs in BACH2 siRNA treated UCB T-cells as compared to control. CD3/CD28 stimulated untransfected UCB T-cells were previously shown to have decrease expression of NFAT1, JunB, FosL1, IFN-γ, and TNF-α, and in UCB T-cells compared to stimulated AB T-cells. Conclusions: BACH2 expression correlates with an inhibition of expression of AP1 transcription regulatory proteins in UCB T-cells during primary CD3/CD28 stimulation. The complete activation of the T-cell requires the activation of AP1 by CD28 pathway otherwise the antigen presenting cell signals the T-cell to enter anergy. In UCB CD4+ T-cells express BACH2, which acts as a transcriptional inhibitor of two critical AP1 genes, JUNB and FosL1, which mediate the CD28 co-stimulatory pathway. These results further suggests that expression of BACH2 in UCB T-cells may contribute to lower incidence of alloreactivity observed in leukemia patients receiving UCB stem cells compared to AB bone marrow stem cells and thus leads to low GVHD, and contribute to the weak Th1 response seen in stimulated UCB T-cells by reduced amounts of AP1 protein available for activating the T-cell.

Study on Mechanism of Human Marrow Mesenchymal Stem Cell in Treating Patients with Aplastic Anemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4099-4099
Author(s):  
Zhenhua Qiao ◽  
Xiujuan Zhao
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
T Cells ◽  
Aplastic Anemia ◽  
Hematopoietic Cell ◽  
Control Group ◽  
Rt Pcr ◽  
Tnf Α ◽  
Ifn Γ ◽  
Tgf Β1

Abstract Objective: To explore mechanism of human marrow mesenchymal stem cells (MSCs) in treating patients with aplastic anemia(AA). Methods: MSCs in patients with aplastic anemia(AA) and the control group were separated with Percoll(1.073g/m L) and cultured in low glucose DMEM. Then, observed their morphologies,checked their molecule surface antigen by flow cytometry and examined the process of adipogenic differention. The mononuclear cells (MNC)of marrow in patients with AA were enriched based 1.077g/L density centrifuge and cultured in the 1640 medium. (1)MSC in control group and MNC in AA group were co-cultured with or without cytokines. The function of supporting hematopoiesis for MSC was to be observed in single confluence layer after plating by counting the total cells and the clones in every well every week. Then analyzed the dynamics of proliferation. T cells were harvested by using nylon column. MSC in control group and T cells in AA group were co-cultured. The proliferation of T cell was measured by MTT method. The CD25,CD69,CD4,CD8,Annexin-V expression rates of CD3+T cells were analyzed by flow cytometry .The gene and protein of IL-2, IL-4,IL-10,TNF-α,IFN-γ,TGF-β1 were examined by RT-PCR and ELISA respectively. MSC treated to the model of AA, by the examination of peripheral hemogram, bone marrow biopsy, pathological section of spleen. Results: There was no significant difference between control group MSC and AA-MSC in morphologies but adipogenic differentiation in AA patients is earlier than controls. The clones of CFU-GM in group(MSC)(78.46±3.58)/2×105 cells, after 14 days cultured was significantly higher than(9.21±4.32)/2×105 cells in group(CK + DMEM medium), while lower than (99.32±4.34)/2×105 cells in group(MSC+CK). (1)the Treg cells (TCD4+CD25+) in AA group (2.01±1.21)/ 2×105 was significantly lower than (4.43±1.67)/2×105 cells in control group, while(5.43±2.31) / 2×105 in group (MSC+AAT) was no more than (4.43±1.67)/2×105 cells in control group. (2) MSCs significantly inhibited T cell proliferation (P< 0. O5)by MTT. (3) RT-PCR and ELISA analysis showed that MSCs induced the expression of IL-4, IL-10, TGF-β1 and decreased significantly the expression of IL-2, TNF-α, IFN -γ in T cells of AA. the model of AA treated by MSCs showed improvements in 3 blood components greatly(p<0.05), Bone marrow proliferated and restored to the normal level, hematopoietic cell increased obviously (hematopoietic cell capacity was more than 40%), and atrophied spleen restore to normality. Conclusions: morphologies of AA’MSC had no evident different with the control but was more easy adipogenic differention. aplastic anemia belongs to autoimmune diseases in which T cells effect organ-specific destruction. The fundamental mechanism of MSC in treating AA should be potential to promote hematopoietic cell proliferation by adjusting immunity.

Aspirin Blocks Orthodontic Relapse via Inhibition of CD4+ T Lymphocytes

2017 ◽  
Vol 96 (5) ◽  
pp. 586-594 ◽  
Author(s):  
Y. Liu ◽  
T. Zhang ◽  
C. Zhang ◽  
S.S. Jin ◽  
R.L. Yang ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Relapse Rate ◽  
Immune Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Th1 Cells ◽  
Tnf Α ◽  
Inflammatory Drugs ◽  
Ifn Γ ◽  
Anti Inflammatory

Immunologic response plays an important role in orthodontic tooth movement (OTM) and relapse. Nonsteroidal anti-inflammatory drugs, such as aspirin, affect immune cells and clinical orthodontic treatment. However, the mechanisms by which nonsteroidal anti-inflammatory drugs regulate immune cells to affect orthodontic relapse are unclear. In this study, male Sprague-Dawley rats were grouped as relapse and relapse + aspirin for 10 d after 14 d of OTM. Silicone impressions of the rats’ maxillary dentitions were obtained to record the distance of OTM at the indicated time point. CD4+ T lymphocytes in spleen were examined by flow cytometry. Serum levels of type 1 T-helper (Th1) cell–associated cytokines tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ) were determined through enzyme-linked immunosorbent assay. The effects of aspirin on CD4+ T and Th1 cells were also analyzed in vitro. Aspirin treatment significantly reduced the relapse rate. More interestingly, injection of CD25 neutralizing antibody basiliximab or TNF-α inhibitor etanercept can significantly reduce the relapse rate as well. Correspondingly, aspirin treatment significantly accelerated the decrease of orthodontic force–induced secretion of TNF-α and IFN-γ in serum and the expression of TNF-α and IFN-γ in periodontal ligament during relapse. Furthermore, aspirin treatment in vitro significantly repressed the differentiation of CD4+ T and Th1 cells. Overall, results indicated that aspirin treatment can block orthodontic relapse by regulating Th1 cells.

scholarly journals Cutaneous Leishmaniasis in Naturally Infected Dogs is Associated with a T Helper-2-biased Immune Response

2005 ◽  
Vol 42 (2) ◽  
pp. 166-175 ◽  
Author(s):  
C. Brachelente ◽  
N. Müller ◽  
M. G. Doherr ◽  
U. Sattler ◽  
M. Welle
Keyword(s):  
Immune Response ◽  
Parasite Burden ◽  
Skin Lesions ◽  
Cytokine Expression ◽  
T Helper ◽  
T Helper 2 ◽  
Th2 Cytokine ◽  
Tnf Α ◽  
Skin Biopsies ◽  
Ifn Γ

Skin lesions are a frequent manifestation of Leishmania infantum infections in Mediterranean countries. This study demonstrates by real-time reverse transcriptase-polymerase chain reaction the local cytokine response in skin biopsies from Leishmania-infected dogs ( n = 10). As controls, we investigated skin biopsies from healthy ( n = 10) and fleabite hypersensitive dogs (n = 10). We established a quantitative PCR to determine the parasite burden in biopsies. The objective was to elucidate whether a correlation exists between parasite number, histologic response, and T helper-1 (TH1)/T helper-2 (TH2) cytokine expression in lesional skin of naturally infected dogs. In Leishmania-infected dogs, interleukin-4 (IL-4), tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) messenger RNA production was significantly higher than controls. Furthermore, dogs with a high Leishmania burden had a significantly higher IL-4 expression, whereas no difference was noted with regard to expression of other cytokines. By comparing the pattern of inflammation and cytokine expression, a clear trend became evident in that levels of IL-4, TNF-α, and IFN-γ were elevated in biopsies with a periadnexal nodular pattern and in biopsies where the severity of the periadnexal infiltrate was equal to the perivascular to interstitial infiltrate. Expression of IL-4, IL-13, and TNF-α was slightly increased in biopsies where plasma cells prevailed on lymphocytes, whereas expression of IFN-γ was moderately higher when lymphocytes were predominating. In summary, the present study demonstrates that the local immune response in naturally occurring leishmaniasis includes TH1 as well as TH2 cytokine subsets. Furthermore, respective data suggest that increased expression of the TH2-type cytokine IL-4 is associated with both severe clinical signs and a high parasite burden in the skin lesions.

scholarly journals Cytokine regulation of stem cells

2016 ◽  
Author(s):  
Gyanesh Singh ◽  
Hasan Korkaya
Keyword(s):  
Stem Cells ◽  
Dendritic Cells ◽  
Stem Cell ◽  
Immune Cells ◽  
Interferon Γ ◽  
Gm Csf ◽  
Cell Functions ◽  
Tnf Α ◽  
Different Types ◽  
Ifn Γ

Different types of stem cells are targeted by a number of cytokines that alter proliferation, differentiation, or other properties of stem cells. Stem cells are known to express various cytokine genes. As IL-12, IL-14, G-CSF, and GM-CSF expression is lost after the differentiation of MSCs, these factors might have major contribution to pluripotency. Several other cytokines that are produced by immune cells, frequently target stem cells. Modulation of stem cell functions by cytokines can be a cause of various diseases including cancer. Stem cells can show immunosuppressive properties by a number of mechanisms. MSC-induced immunosuppression is often mediated by IFN-γ, TNF-α, IL-1α, or IL-1β. In co-culture experiments, MSCs were able to control T cells IL-2 response, or, dendritic cells TNF-α and IL-10 secretion. MSCs are also known to cause decreased interferon γ (IFN-γ) and increased IL-4 production by immune cells. However, the outcome in most of the cases depends on the presence of various factors that might synergize or antagonize with each other.

scholarly journals Association of immunological features with COVID-19 severity: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Zhicheng Zhang ◽  
Guo Ai ◽  
Liping Chen ◽  
Shunfang Liu ◽  
Chen Gong ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Cells ◽  
Nk Cell ◽  
Meta Analysis ◽  
Grey Literature ◽  
Cochrane Library ◽  
Gm Csf ◽  
Tnf Α ◽  
Ifn Γ ◽  
The Cochrane Library

Abstract Background: We aim to explore the association of immunological features with COVID-19 severity.Methods: We conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed, Web of Science, Scopus, the Cochrane Library and the grey literature.Results: A total of 21 studies with 2033 COVID-19 patients were included. Compared with mild cases, severe cases showed significantly lower levels of some immune cells, CD3+ T cell (×106, MD, -413.87; 95%CI, -611.39 to -216.34), CD4+ T cell (×106, MD, -203.56; 95%CI, -277.94 to -129.18), CD8+ T cell (×106, MD, -128.88; 95%CI, -163.97 to -93.79), B cell (×106/L; MD, -23.87; 95%CI, -43.97 to -3.78) and NK cell (×106/L; MD, -57.12; 95%CI, -81.18 to -33.06), and significantly higher levels of some cytokines, TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75), and significantly higher levels of some chemokines, MCP-1 (SMD, 3.41; 95%CI, 2.42 to 4.40), IP-10 (SMD, 2.82; 95%CI, 1.20 to 4.45) and eotaxin (SMD, 1.55; 95%CI, 0.05 to 3.05). However, no significant differences were found in other indicators, Treg cell (×106, MD, -0.13; 95%CI, -1.40 to 1.14), CD4+/CD8+ ratio (MD, 0.26; 95%CI, -0.02 to 0.55), IFN-γ (pg/ml; MD, 0.26; 95%CI, -0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, -0.49 to 0.60), IL-4 (pg/ml; MD, -0.03; 95%CI, -0.68 to 0.62), GM-CSF (SMD, 0.44; 95%CI, -0.46 to 1.35), and RANTES (SMD, 0.94; 95%CI, -2.88 to 4.75).Conclusion: Our meta-analysis revealed significant lower levels of immune cells (CD3+ T, CD4+ T, CD8+ T, B and NK cells), significant higher levels of cytokines (TNF-α, IL-5, IL-6 and IL-10) and significant higher levels of chemokines (MCP-1, IP-10 and eotaxin) in severe cases compared with mild cases of COVID-19. Measurement of immunological features could help to assess disease severity for effective triage of COVID-19 patients.

scholarly journals Alteration of Colonic Mucosal Permeability during Antibiotic-Induced Dysbiosis

2020 ◽  
Vol 21 (17) ◽  
pp. 6108
Author(s):  
Ying Ran ◽  
Hirokazu Fukui ◽  
Xin Xu ◽  
Xuan Wang ◽  
Nobuhiko Ebisutani ◽  
...  
Keyword(s):  
Colonic Mucosa ◽  
Polymyxin B ◽  
Mucosal Barrier ◽  
Rt Pcr ◽  
Mucosal Permeability ◽  
16S Rrna Analysis ◽  
Caco2 Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Microbiota Diversity

Although dysbiosis is likely to disturb the mucosal barrier system, the mechanism involved has remained unclear. Here, we investigated alterations of colonic mucosal permeability and tight junction (TJ) molecules in mice with antibiotic-induced dysbiosis. Mice were orally administered vancomycin or polymyxin B for 7 days, and then fecal samples were subjected to microbial 16S rRNA analysis. The colonic mucosal permeability was evaluated by chamber assay. The colonic expression of TJ molecules and cytokines was examined by real-time RT-PCR, Western blotting, and immunohistochemistry. Caco2 cells were stimulated with cytokines and their transepithelial electric resistance (TEER) was measured. Vancomycin-treated mice showed significantly lower gut microbiota diversity than controls, and the same tendency was evident in polymyxin B-treated mice. The colonic mucosal permeability was significantly elevated in both vancomycin- and polymyxin B-treated mice. The expression of claudin 4 in the colonic mucosa was decreased in both vancomycin- and polymyxin B-treated mice. Colonic expression of TNF-α and/or IFN-γ was significantly increased in mice that had been administered antibiotics. TNF-α and IFN-γ stimulation dose-dependently decreased TEER in Caco2 cells. Antibiotic-induced dysbiosis is correlated with the enhancement in colonic tissue permeability, accompanied by a reduction in claudin 4 expression and enhancement in TNF-α and/or IFN-γ expression in mice.

Sign in / Sign up

Export Citation Format

Share Document