Acute stressor exposure both suppresses acquired immunity and potentiates innate immunity

1998 ◽  
Vol 275 (3) ◽  
pp. R870-R878 ◽  
Author(s):  
Monika Fleshner ◽  
Kien T. Nguyen ◽  
Crystal S. Cotter ◽  
Linda R. Watkins ◽  
Steven F. Maier
Keyword(s):  
Keyhole Limpet Hemocyanin ◽  
Interferon Γ ◽  
Cell Number ◽  
Antigenic Protein ◽  
Nitrite Production ◽  
Ifn Γ ◽  
Cell Subpopulations ◽  
T Cell Subpopulations ◽  
Acute Stressor ◽  
Increase Cell Number

Acute stressor exposure alters immune function. Rats exposed to inescapable tail shock stress (IS) generate less antibody to a benign, antigenic protein, keyhole limpet hemocyanin (KLH). The following studies examined the effect of IS on peritoneal cavity, spleen, and mesenteric lymph node cell number, interferon-γ (IFN-γ) production, and nitrite production. Rats were injected intraperitoneally with KLH (200 μg) or saline immediately before IS exposure and killed 0, 48, and 96 h after IS termination. KLH immunization resulted in elevated cell numbers and IFN-γ levels 2–4 days later in nonstressed control rats. In contrast, rats exposed to IS failed to increase cell number and IFN-γ levels in response to KLH. The T cell subpopulations affected were CD4 T cells, specifically the Th1-like subset. In addition, in rats exposed to IS + KLH, nitrite production was potentiated 2–4 days after stressor termination. IS had little effect on these measures in saline-injected rats. These data support the conclusion that exposure to IS suppresses the expansion of anti-KLH lymphocytes, possibly anti-KLH Th1 cells. In addition, stressor exposure potentiates the production of nitrite. Importantly, this potentiated response occurred only in KLH-immunized animals, suggesting that macrophages may be primed by stressor exposure and thus respond more vigorously to antigen. The potential links between these changes are discussed.

scholarly journals Immunomodulatory Effects of Phosphorylated Radix Cyathulae officinalis Polysaccharides in Immunosuppressed Mice

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4150 ◽  
Author(s):  
Feng ◽  
Fan ◽  
Lin ◽  
Liu ◽  
Chai ◽  
...  
Keyword(s):  
Serum Levels ◽  
Peritoneal Macrophages ◽  
Splenocyte Proliferation ◽  
Immunomodulatory Effects ◽  
Humoral Immune ◽  
Ifn Γ ◽  
Cell Subpopulations ◽  
Cellular And Humoral Immunity ◽  
T Cell Subpopulations ◽  
Immunosuppressed Mice

This research aimed to investigate the immunomodulatory effects of phosphorylated Radix Cyathulae officinalis Kuan polysaccharides (pRCPS) in immunosuppressed mice, improving their cellular and humoral immune function. Our results showed that pRCPS increased serum immunoglobulin (IgG, IgA, IgM) concentrations significantly, enhanced splenocyte proliferation, and the thymus and spleen indices. pRCPS also promoted phagocytosis in peritoneal macrophages and enhanced cytokine (IFN-γ, IL-2, -4, -5, -6, and -10) serum levels. Importantly, pRCPS increased the proportions of selected T cell subpopulations (CD3+, CD4+, and the CD4+ to CD8+ ratio). Our results revealed that phosphorylation of the polysaccharides promoted their immune-enhancing effects. Thus, pRCPS can enhance cellular and humoral immunity and could be used as an immune-enhancing agent to overcome cyclophosphamide (CY)-induced immunosuppression.

Activation of purinergic P2Y2 receptors inhibits inducible NO synthase in cultured rat mesangial cells

1998 ◽  
Vol 275 (1) ◽  
pp. F103-F110 ◽  
Author(s):  
Markus G. Mohaupt ◽  
Tina Fischer ◽  
Jörg Schwöbel ◽  
R. Bernd Sterzel ◽  
Eckhard Schulze-Lohoff
Keyword(s):  
Mesangial Cells ◽  
Critical Role ◽  
Inhibitory Effect ◽  
Interferon Γ ◽  
Glomerular Injury ◽  
Inos Protein ◽  
P2y2 Receptors ◽  
Nitrite Production ◽  
Inos Protein Expression ◽  
Ifn Γ

Cytokine-induced nitric oxide (NO) is produced on glomerular inflammation. Glomerular injury and thrombocyte aggregation result in the release of nucleotides, which may regulate induced NO synthesis in cultured rat mesangial cells (MCs). ATP (10−3 M) inhibited 24-h nitrite production induced by lipopolysaccharide (LPS, 10 μg/ml)/interferon-γ (IFN-γ, 100 U/ml) by 48.2 ± 6.3%, as well as induction of inducible NOS (iNOS) protein and mRNA. Also, coincubation with either 10−4 M of UTP, ATP, or ATPγS inhibited LPS/IFN-γ-induced nitrite production by 29.9 ± 5.8, 36.4 ± 4.3, and 50.3 ± 6.5%, respectively, indicating involvement of purinergic P2Y2 receptors. Correspondingly, cultured MCs expressed P2Y2 receptor mRNA. Agonists for other purinergic receptors [α,β-methylene-ATP, 3′- O-(4-benzoyl)-benzoyl-ATP, 2-methylthio-ATP, ADP, UDP, adenosine] were ineffective. Treatment with the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 10−8 M) reproduced the inhibitory effect of ATP on iNOS protein expression and nitrite inhibition (by 46.6 ± 10.4%). The effect of ATP or PMA was reversed by the PKC inhibitors Ro-31-8220 (10−8 M) and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (10−5 M), indicating that suppression of iNOS is mediated via activation of PKC through stimulated P2Y2 receptors. In conclusion, the release of purine mediators may play a critical role for iNOS expression and synthesis of NO during glomerular inflammatory disorders.

scholarly journals Fasting-induced intestinal apoptosis is mediated by inducible nitric oxide synthase and interferon-γ in rat

2010 ◽  
Vol 298 (6) ◽  
pp. G916-G926 ◽  
Author(s):  
Junta Ito ◽  
Hiroyuki Uchida ◽  
Takayuki Yokote ◽  
Kazuo Ohtake ◽  
Jun Kobayashi
Keyword(s):  
Nitric Oxide ◽  
Protein Expression ◽  
Interferon Γ ◽  
No Synthase ◽  
Histological Evaluation ◽  
No Production ◽  
Ros Production ◽  
Nitrite Production ◽  
Ifn Γ

Nitric oxide (NO) is associated with intestinal apoptosis in health and disease. This study aimed to investigate the role of intestinal NO in the regulation of apoptosis during fasting in rats. Male Wistar rats were divided into two groups and subcutaneously injected with saline (SA) or aminoguanidine (AG), followed by fasting for 24, 48, 60, and 72 h. At each time point, the jejunum was subjected to histological evaluation for enterocyte apoptosis by histomorphometric assessment and TUNEL analysis. We performed immunohistochemistry for inducible NO synthase (iNOS) expression in the jejunum and measured tissue nitrite levels using HPLC and 8-hydroxydeoxyguanosine adduct using ELISA, indicative of endogenous NO production and reactive oxygen species (ROS) production, respectively. Jejunal transcriptional levels of iNOS, neuronal NO synthase (nNOS), and interferon-γ (IFN-γ) were also determined by RT-PCR. Fasting caused significant jejunal mucosal atrophy due to attenuated cell proliferation and enhanced apoptosis with increase in iNOS transcription, its protein expression in intestinal epithelial cells (IEC), and jejunal nitrite levels. However, AG treatment histologically reduced apoptosis with inhibition of fasting-induced iNOS transcription, protein expression, and nitrite production. We also observed fasting-induced ROS production and subsequent IFN-γ transcription, which were all inhibited by AG treatment. Furthermore, we observed reduced transcriptional levels of nNOS, known to suppress iNOS activation physiologically. These results suggest that fasting-induced iNOS activation in IEC may induce apoptosis mediators such as IFN-γ via a ROS-mediated mechanism and also a possible role of nNOS in the regulation of iNOS activity in fasting-induced apoptosis.

scholarly journals Natural History and Evolution of Anti-Interferon-γ Autoantibody-Associated Immunodeficiency Syndrome in Thailand and the United States

2019 ◽  
Vol 71 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Gloria H Hong ◽  
Ana M Ortega-Villa ◽  
Sally Hunsberger ◽  
Ploenchan Chetchotisakd ◽  
Siriluck Anunnatsiri ◽  
...  
Keyword(s):  
United States ◽  
Natural History ◽  
The United States ◽  
Interferon Γ ◽  
Mycobacterium Abscessus ◽  
Annual Data ◽  
Persistent Infections ◽  
Ifn Γ ◽  
Immunodeficiency Syndrome

Abstract Background The natural history of anti-interferon-γ (IFN-γ) autoantibody-associated immunodeficiency syndrome is not well understood. Methods Data of 74 patients with anti-IFN-γ autoantibodies at Srinagarind Hospital, Thailand, were collected annually (median follow-up duration, 7.5 years). Annual data for 19 patients and initial data for 4 patients with anti-IFN-γ autoantibodies at the US National Institutes of Health were collected (median follow-up duration, 4.5 years). Anti-IFN-γ autoantibody levels were measured in plasma samples. Results Ninety-one percent of US patients were of Southeast Asian descent; there was a stronger female predominance (91%) in US than Thai (64%) patients. Mycobacterium abscessus (34%) and Mycobacterium avium complex (83%) were the most common nontuberculous mycobacteria in Thailand and the United States, respectively. Skin infections were more common in Thailand (P = .001), whereas bone (P < .0001), lung (P = .002), and central nervous system (P = .03) infections were more common in the United States. Twenty-four percent of Thai patients died, most from infections. None of the 19 US patients with follow-up data died. Anti-IFN-γ autoantibody levels decreased over time in Thailand (P < .001) and the United States (P = .017), with either cyclophosphamide (P = .01) or rituximab therapy (P = .001). Conclusions Patients with anti-IFN-γ autoantibodies in Thailand and the United States had distinct demographic and clinical features. While titers generally decreased with time, anti-IFN-γ autoantibody disease had a chronic clinical course with persistent infections and death. Close long-term surveillance for new infections is recommended.

scholarly journals The Role of Interleukine-10 and Interferon-γ as Potential Markers of the Evolution of African Swine Fever Virus Infection in Wild Boar

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 757
Author(s):  
Sandra Barroso-Arévalo ◽  
Jose A. Barasona ◽  
Estefanía Cadenas-Fernández ◽  
José M. Sánchez-Vizcaíno
Keyword(s):  
Wild Boar ◽  
Vaccine Candidate ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Interferon Γ ◽  
Fever Virus ◽  
Control Group ◽  
Challenge Virus ◽  
Ifn Γ

African swine fever virus (ASFv) is one of the most challenging pathogens to affect both domestic and wild pigs. The disease has now spread to Europe and Asia, causing great damage to the pig industry. Although no commercial vaccine with which to control the disease is, as yet, available, some potential vaccine candidates have shown good results in terms of protection. However, little is known about the host immune mechanisms underlying that protection, especially in wild boar, which is the main reservoir of the disease in Europe. Here, we study the role played by two cytokines (IL-10 and IFN-γ) in wild boar orally inoculated with the attenuated vaccine candidate Lv17/WB/Rie1 and challenged with a virulent ASFv genotype II isolate. A group of naïve wild boar challenged with the latter isolate was also established as a control group. Our results showed that both cytokines play a key role in protecting the host against the challenge virus. While high levels of IL-10 in serum may trigger an immune system malfunctioning in challenged animals, the provision of stable levels of this cytokine over time may help to control the disease. This, together with high and timely induction of IFN-γ by the vaccine candidate, could help protect animals from fatal outcomes. Further studies should be conducted in order to support these preliminary results and confirm the role of these two cytokines as potential markers of the evolution of ASFV infection.

scholarly journals Regulatory T Cell-Enhancing Therapies to Treat Atherosclerosis

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 723
Author(s):  
Hafid Ait-Oufella ◽  
Jean-Rémi Lavillegrand ◽  
Alain Tedgui
Keyword(s):  
T Cell ◽  
Current Knowledge ◽  
Experimental Studies ◽  
Therapeutic Approaches ◽  
Coronary Patients ◽  
Cell Subpopulations ◽  
Atherosclerotic Process ◽  
T Cell Subpopulations ◽  
Disease Analysis

Experimental studies have provided strong evidence that chronic inflammation triggered by the sub-endothelial accumulation of cholesterol-rich lipoproteins in arteries is essential in the initiation and progression of atherosclerosis. Recent clinical trials highlighting the efficacy of anti-inflammatory therapies in coronary patients have confirmed that this is also true in humans Monocytes/macrophages are central cells in the atherosclerotic process, but adaptive immunity, through B and T lymphocytes, as well as dendritic cells, also modulates the progression of the disease. Analysis of the role of different T cell subpopulations in murine models of atherosclerosis identified effector Th1 cells as proatherogenic, whereas regulatory T cells (Tregs) have been shown to protect against atherosclerosis. For these reasons, better understanding of how Tregs influence the atherosclerotic process is believed to provide novel Treg-targeted therapies to combat atherosclerosis. This review article summarizes current knowledge about the role of Tregs in atherosclerosis and discusses ways to enhance their function as novel immunomodulatory therapeutic approaches against cardiovascular disease.

scholarly journals THU0052 RELATIONSHIP BETWEEN INTERFERON-Γ-PRODUCING IMMUNOCOMPETENT CELLS AND DISEASE ACTIVITY IN ADULT-ONSET STILL’S DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 238.1-238
Author(s):  
Y. Shimojima ◽  
D. Kishida ◽  
T. Ichikawa ◽  
Y. Sekijima
Keyword(s):  
T Cells ◽  
Disease Activity ◽  
Nk Cells ◽  
Acute Phase ◽  
Serum Ferritin ◽  
Interferon Γ ◽  
Adult Onset Still’S Disease ◽  
Still’S Disease ◽  
Ifn Γ ◽  
Adult Onset Still's Disease

Background:In the acute phase of adult-onset Still’s disease (AOSD), elevated levels of proinflammatory cytokines including interferon-γ (IFN-γ) are shown. Moreover, IFN-γ impacts on activating macrophages which play a crucial role in the pathogenesis of AOSD. Natural killer (NK) cells and T helper cells are in charge of secreting IFN-γ in the innate and adaptive immune systems of disease, respectively. However, the features of their IFN-γ-producing variation depending on disease activity are still uncertain in AOSD.Objectives:We investigated characteristics of IFN-γ-producing CD4+T cells and NK cells in patients with AOSD.Methods:Twenty-four patients in the acute phase of AOSD (active AOSD), 8 of them after treatment (remission), and 12 healthy controls (HC) were recruited in this study. Peripheral blood mononuclear cells and serum samples were provided from them for the experimental analysis. Flow cytometry was used for analyzing CD4+T cells, CD4+regulatory T cells (Tregs), NK cells, and their intracellular IFN-γ expression levels as well as suppression assay of Tregs. The serum concentration of interleukin-18 (IL-18) was measured using commercially available ELISA kit. Relationship between the analyzed data and clinical findings related to disease activity were statistically evaluated.Results:IFN-γ expression in CD4+T cells was significantly higher in active AOSD than in HC (p < 0.05). Tregs also significantly indicated higher expression of IFN-γ in active AOSD than in HC (p < 0.0001); and moreover, Tregs were significantly impaired in their suppression ability (p < 0.05). In both CD4+T cells and Tregs, expression of IFN-γ was significantly correlated with serum ferritin levels in active AOSD (p < 0.05). IFN-γ expression in CD4+T cells was significantly higher in patients with splenomegaly than those without that (p < 0.05). The proportion of NK cells was significantly lower in active AOSD than in HC (p < 0.005), whereas IFN-γ expression in NK cells was significantly higher in active AOSD than in HC (p < 0.0005). The number of NK cells and IFN-γ-expressing NK cells had inverse relationship with serum ferritin levels in active AOSD (p < 0.05 and p < 0.005, respectively). Increased number of NK cells and their decreased expression of IFN-γ were significantly demonstrated in remission (p < 0.05). In the analyses of NK cell subsets, lower expression of IFN-γ in CD56brightNK cells and higher that in CD56dimNK cells were significantly indicated in active AOSD than HC (p < 0.05). In remission, IFN-γ expression was significantly decreased in CD56dimNK cells (p < 0.05) despite no significant recovery of that in CD56brightNK cells (p = 0.311). Meanwhile, increased expression of IFN-γ in CD56brightNK cells was demonstrated in only patients who were treated with biologics. Although serum levels of IL-18 were significantly higher in active AOSD than in remission and HC; however, they had no significant correlations with any analyzed data.Conclusion:CD4+T cells and NK cells promote IFN-γ expression in the acute phase of AOSD. Meanwhile, increased expression of IFN-γ in CD4+T cells and decreased number of NK cells were correlated with serum ferritin levels, suggesting that they are indicators of disease activity. Furthermore, high disease activity may impact on the alteration of IFN-γ-producing balance in two distinct population of NK cells, and the plasticity of Tregs leading to defect in suppression ability.Disclosure of Interests:None declared

scholarly journals Adult Renal Stem/Progenitor Cells Can Modulate T Regulatory Cells and Double Negative T Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 274
Author(s):  
Claudia Curci ◽  
Angela Picerno ◽  
Nada Chaoul ◽  
Alessandra Stasi ◽  
Giuseppe De Palma ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Double Negative ◽  
Chronic Injury ◽  
Peripheral Blood Mononuclear ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

Adult Renal Stem/Progenitor Cells (ARPCs) have been recently identified in the human kidney and several studies show their active role in kidney repair processes during acute or chronic injury. However, little is known about their immunomodulatory properties and their capacity to regulate specific T cell subpopulations. We co-cultured ARPCs activated by triggering Toll-Like Receptor 2 (TLR2) with human peripheral blood mononuclear cells for 5 days and 15 days and studied their immunomodulatory capacity on T cell subpopulations. We found that activated-ARPCs were able to decrease T cell proliferation but did not affect CD8+ and CD4+ T cells. Instead, Tregs and CD3+ CD4- CD8- double-negative (DN) T cells decreased after 5 days and increased after 15 days of co-culture. In addition, we found that PAI1, MCP1, GM-CSF, and CXCL1 were significantly expressed by TLR2-activated ARPCs alone and were up-regulated in T cells co-cultured with activated ARPCs. The exogenous cocktail of cytokines was able to reproduce the immunomodulatory effects of the co-culture with activated ARPCs. These data showed that ARPCs can regulate immune response by inducing Tregs and DN T cells cell modulation, which are involved in the balance between immune tolerance and autoimmunity.

Regulation of mouse natural killer (NK) activity by interferon-γ (IFN-γ)

1985 ◽  
Vol 7 (3) ◽  
pp. 327
Author(s):  
F. Velotti ◽  
A. Santoni ◽  
F. Cofano ◽  
S. Landolfo ◽  
M. Piccoli ◽  
...  
Keyword(s):  
Natural Killer ◽  
Interferon Γ ◽  
Nk Activity ◽  
Ifn Γ
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