scholarly journals Altered Ex-Vivo Cytokine Responses in Children With Asymptomatic Plasmodium falciparum Infection in Burkina Faso: An Additional Argument to Treat Asymptomatic Malaria?

2021 ◽  
Vol 12 ◽  
Author(s):  
Annelies Post ◽  
Berenger Kaboré ◽  
Mike Berendsen ◽  
Salou Diallo ◽  
Ousmane Traore ◽  
...  
Keyword(s):  
Whole Blood ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Clinical Malaria ◽  
Innate Immune ◽  
Asymptomatic Malaria ◽  
Cytokine Responses ◽  
Tnf Α ◽  
Ifn Γ ◽  
Malaria Microscopy

IntroductionPatients with clinical malaria have an increased risk for bacterial bloodstream infections. We hypothesized that asymptomatic malaria parasitemia increases susceptibility for bacterial infections through an effect on the innate immune system. We measured circulating cytokine levels and ex-vivo cytokine production capacity in asymptomatic malaria and compared with controls.MethodsData were collected from asymptomatic participants <5 years old with and without positive malaria microscopy, as well as from hospitalized patients <5 years old with clinical malaria, bacteremia, or malaria/bacteremia co-infections in a malaria endemic region of Burkina Faso. Circulating cytokines (TNF-α, IFN-γ, IL-6, IL-10) were measured using multiplex assays. Whole blood from asymptomatic participants with and without positive malaria microscopy were ex-vivo stimulated with S. aureus, E. coli LPS and Salmonella Typhimurium; cytokine concentrations (TNF-α, IFN-γ, IL-1β, IL-6, IL-10) were measured on supernatants using ELISA.ResultsIncluded were children with clinical malaria (n=118), bacteremia (n=22), malaria and bacteremia co-infection (n=9), asymptomatic malaria (n=125), and asymptomatic controls (n=237). Children with either clinical or asymptomatic malaria had higher plasma cytokine concentrations than controls. Cytokine concentrations correlated positively with malaria parasite density with the strongest correlation for IL-10 in both asymptomatic (r=0.63) and clinical malaria (r=0.53). Patients with bacteremia had lower circulating IL-10, TNF-α and IFN-γ and higher IL-6 concentrations, compared to clinical malaria. Ex-vivo whole blood cytokine production to LPS and S. aureus was significantly lower in asymptomatic malaria compared to controls. Whole blood IFN-γ and IL-10 production in response to Salmonella was also lower in asymptomatic malaria.InterpretationIn children with asymptomatic malaria, cytokine responses upon ex-vivo bacterial stimulation are downregulated. Further studies are needed to explore if the suggested impaired innate immune response to bacterial pathogens also translates into impaired control of pathogens such as Salmonella spp.

scholarly journals Changes in Antigen-Specific Cytokine and Chemokine Responses to Plasmodium falciparum Antigens in a Highland Area of Kenya after a Prolonged Absence of Malaria Exposure

2014 ◽  
Vol 82 (9) ◽  
pp. 3775-3782 ◽  
Author(s):  
Lyticia A. Ochola ◽  
Cyrus Ayieko ◽  
Lily Kisia ◽  
Ng'wena G. Magak ◽  
Estela Shabani ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Disease ◽  
Clinical Malaria ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Highland Area ◽  
Cytokine Responses ◽  
Increased Risk ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACTIndividuals naturally exposed toPlasmodium falciparumlose clinical immunity after a prolonged lack of exposure.P. falciparumantigen-specific cytokine responses have been associated with protection from clinical malaria, but the longevity ofP. falciparumantigen-specific cytokine responses in the absence of exposure is not well characterized. A highland area of Kenya with low and unstable malaria transmission provided an opportunity to study this question. The levels of antigen-specific cytokines and chemokines associated in previous studies with protection from clinical malaria (gamma interferon [IFN-γ], interleukin-10 [IL-10], and tumor necrosis factor alpha [TNF-α]), with increased risk of clinical malaria (IL-6), or with pathogenesis of severe disease in malaria (IL-5 and RANTES) were assessed by cytometric bead assay in April 2008, October 2008, and April 2009 in 100 children and adults. During the 1-year study period, none had an episode of clinicalP. falciparummalaria. Two patterns of cytokine responses emerged, with some variation by antigen: a decrease at 6 months (IFN-γ and IL-5) or at both 6 and 12 months (IL-10 and TNF-α) or no change over time (IL-6 and RANTES). These findings document thatP. falciparumantigen-specific cytokine responses associated in prior studies with protection from malaria (IFN-γ, TNF-α, and IL-10) decrease significantly in the absence ofP. falciparumexposure, whereas those associated with increased risk of malaria (IL-6) do not. The study findings provide a strong rationale for future studies of antigen-specific IFN-γ, TNF-α, and IL-10 responses as biomarkers of increased population-level susceptibility to malaria after prolonged lack ofP. falciparumexposure.

Increase in cytokine production (IL-1β, IL-6, TNF-α but not IFN-γ, GM-CSF or LIF) by stimulated whole blood cells in postmenopausal osteoporosis

Maturitas ◽  
1997 ◽  
Vol 26 (1) ◽  
pp. 63-71 ◽  
Author(s):  
S.X. Zheng ◽  
Y. Vrindts ◽  
M. Lopez ◽  
D. De Groote ◽  
P.F. Zangerle ◽  
...  
Keyword(s):  
Postmenopausal Osteoporosis ◽  
Whole Blood ◽  
Blood Cells ◽  
Cytokine Production ◽  
Gm Csf ◽  
Tnf Α ◽  
Ifn Γ ◽  
Whole Blood Cells

scholarly journals Ex Vivo Cytokine Release, Determined by a Multiplex Cytokine Assay, in Response to Coccidioidal Antigen Stimulation of Whole Blood among Subjects with Recently Diagnosed Primary Pulmonary Coccidioidomycosis

mSphere ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Neil M. Ampel ◽  
Ian Robey ◽  
Chinh T. Nguyen ◽  
Brentin Roller ◽  
Jessica August ◽  
...  
Keyword(s):  
Antifungal Therapy ◽  
Whole Blood ◽  
Ex Vivo ◽  
Valley Fever ◽  
Blood Samples ◽  
Antigen Stimulation ◽  
Gm Csf ◽  
Tnf Α ◽  
Inflammatory Proteins ◽  
Ifn Γ

ABSTRACT The elements of the cellular immune response in human coccidioidomycosis remain undefined. We examined the ex vivo release of an array of inflammatory proteins in response to incubation with a coccidioidal antigen preparation to ascertain which of these might be associated with diagnosis and outcome. Patients with a recent diagnosis of primary pulmonary coccidioidomycosis and a control group of healthy subjects were studied. Blood samples were incubated for 18 h with T27K, a soluble coccidioidal preparation containing multiple glycosylated antigens, and the supernatant was assayed for inflammatory proteins using the multiplex Luminex system. The presentation and course of illness were compared to the levels of the inflammatory proteins. Among the 31 subjects studied, the median time from diagnosis to assay was 15 days. Of the 30 inflammatory proteins measured, the levels of only 7 proteins, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 receptor alpha (IL-1RA), interleukin-1β (IL-1β), interferon gamma (IFN-γ), IL-2, IL-13, and tumor necrosis factor alpha (TNF-α), were more than 10-fold above the levels seen without antigen stimulation. The levels of IFN-γ and IL-2 were significantly elevated in those subjects not receiving triazole antifungal therapy compared to those who were receiving triazole antifungal therapy. While the levels of IL-1RA were nonspecifically elevated, elevated levels of IL-13 were seen only in those with active pulmonary coccidioidomycosis. Only six cytokines were specifically increased in subjects with recently diagnosed primary pulmonary coccidioidomycosis. While IFN-γ, IL-2, and TNF-α have been previously noted, the finding of elevated levels of the innate cytokines GM-CSF and IL-1β could suggest that these, as well as IL-13, are early and specific markers for pulmonary coccidioidomycosis. IMPORTANCE Coccidioidomycosis, commonly known as Valley fever, is a common pneumonia in the southwestern United States. In this paper, we examined the release of 30 inflammatory proteins in whole-blood samples obtained from persons with coccidioidal pneumonia after the blood samples were incubated with a preparation made from the causative fungus, Coccidioides . We found that six of these proteins, all cytokines, were specifically released in high concentrations in these patients. Three of the cytokines were seen very early in disease, and an assay for all six might serve as a marker for the early diagnosis of Valley fever.

scholarly journals Spontaneous Cytokine Production and Its Effect on Induced Production

2002 ◽  
Vol 9 (5) ◽  
pp. 1049-1056 ◽  
Author(s):  
Derrick Walker ◽  
Janine Jason ◽  
Kelly Wallace ◽  
Justin Slaughter ◽  
Virginia Whatley ◽  
...  
Keyword(s):  
T Cells ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Healthy Adults ◽  
Multiparameter Flow Cytometry ◽  
Parasitic Infections ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Cytokines regulate cellular immune activity and are produced by a variety of cells, especially lymphocytes, monocytes, and macrophages. Multiparameter flow cytometry is often used to examine cell-specific cytokine production after in vitro phorbol 12-myristate 13-acetate and ionomycin induction, with brefeldin A or other agents added to inhibit protein secretion. Spontaneous ex vivo production reportedly rarely occurs. We examined the spontaneous production of interleukin 2 (IL-2), IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) by peripheral-blood B lymphocytes, T cells, CD8− T cells, CD8+ T cells, CD3− CD16/56+ lymphocytes (natural killer [NK] cells), CD3+ CD16/56+ lymphocytes (natural T [NT] cells), and/or monocytes of 316 acutely ill hospitalized persons and 62 healthy adults in Malawi, Africa. We also evaluated the relationship between spontaneous and induced cytokine production. In patients, spontaneous TNF-α production occurred most frequently, followed in descending order by IFN-γ, IL-8, IL-4, IL-10, IL-6, and IL-2. Various cells of 60 patients spontaneously produced TNF-α; for 12 of these patients, TNF-α was the only cytokine produced spontaneously. Spontaneous cytokine production was most frequent in the immunoregulatory cells, NK and NT. For IL-2, IL-4, IL-6, IL-8, and IL-10, spontaneous cytokine production was associated with greater induced production. For TNF-α and IFN-γ, the relationships varied by cell type. For healthy adults, IL-6 was the cytokine most often produced spontaneously. Spontaneous cytokine production was not unusual in these acutely ill and healthy persons living in an area where human immunodeficiency virus, mycobacterial, malaria, and assorted parasitic infections are endemic. In such populations, spontaneous, as well as induced, cell-specific cytokine production should be measured and evaluated in relation to various disease states.

scholarly journals Phagocytosis of Borrelia burgdorferi and Treponema pallidum Potentiates Innate Immune Activation and Induces Gamma Interferon Production

2007 ◽  
Vol 75 (4) ◽  
pp. 2046-2062 ◽  
Author(s):  
Meagan W. Moore ◽  
Adriana R. Cruz ◽  
Carson J. LaVake ◽  
Amanda L. Marzo ◽  
Christian H. Eggers ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Nk Cells ◽  
Cell Activation ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Treponema Pallidum ◽  
Gamma Interferon ◽  
Innate Immune ◽  
Host Cells ◽  
Ifn Γ

ABSTRACT We examined the interactions of live and lysed spirochetes with innate immune cells. THP-1 monocytoid cells were activated to comparable extents by live Borrelia burgdorferi and by B. burgdorferi and Treponema pallidum lysates but were poorly activated by live T. pallidum. Because THP-1 cells poorly internalized live spirochetes, we turned to an ex vivo peripheral blood mononuclear cell system that would more closely reflect spirochete-mononuclear phagocyte interactions that occur during actual infection. In this system, B. burgdorferi induced significantly greater monocyte activation and inflammatory cytokine production than did borrelial lysates or T. pallidum, and only B. burgdorferi elicited gamma interferon (IFN-γ) from NK cells. B. burgdorferi was phagocytosed avidly by monocytes, while T. pallidum was not, suggesting that the enhanced response to live B. burgdorferi was due to phagocytosis of the organism. When cytochalasin D was used to block phagocytosis of live B. burgdorferi, cytokine production decreased to levels comparable to those induced by B. burgdorferi lysates, while the IFN-γ response was abrogated altogether. In the presence of human syphilitic serum, T. pallidum was efficiently internalized and initiated responses resembling those observed with live B. burgdorferi, including the production of IFN-γ by NK cells. Depletion of monocytes revealed that they were the primary source of inflammatory cytokines, while dendritic cells (DCs) directed IFN-γ production from innate lymphocytes. Thus, phagocytosis of live spirochetes initiates cell activation programs in monocytes and DCs that differ qualitatively and quantitatively from those induced at the cell surface by lipoprotein-enriched lysates. The greater stimulatory capacity of B. burgdorferi versus T. pallidum appears to be explained by the successful recognition and phagocytosis of B. burgdorferi by host cells and the ability of T. pallidum to avoid detection and uptake by virtue of its denuded outer membrane rather than by differences in surface lipoprotein expression.

scholarly journals Effects of spaceflight on innate immune function and antioxidant gene expression

2009 ◽  
Vol 106 (6) ◽  
pp. 1935-1942 ◽  
Author(s):  
Farnaz P. Baqai ◽  
Daila S. Gridley ◽  
James M. Slater ◽  
Xian Luo-Owen ◽  
Louis S. Stodieck ◽  
...  
Keyword(s):  
Space Shuttle ◽  
Ex Vivo ◽  
Innate Immune ◽  
Oxygen Species ◽  
Bacterial Product ◽  
Th1 Response ◽  
Antioxidant Gene ◽  
Tnf Α ◽  
Antioxidant Gene Expression ◽  
Cell Mitogen

Spaceflight conditions have a significant impact on a number of physiological functions due to psychological stress, radiation, and reduced gravity. To explore the effect of the flight environment on immunity, C57BL/6NTac mice were flown on a 13-day space shuttle mission (STS-118). In response to flight, animals had a reduction in liver, spleen, and thymus masses compared with ground (GRD) controls ( P < 0.005). Splenic lymphocyte, monocyte/macrophage, and granulocyte counts were significantly reduced in the flight (FLT) mice ( P < 0.05). Although spontaneous blastogenesis of splenocytes in FLT mice was increased, response to lipopolysaccharide (LPS), a B-cell mitogen derived from Escherichia coli, was decreased compared with GRD mice ( P < 0.05). Secretion of IL-6 and IL-10, but not TNF-α, by LPS-stimulated splenocytes was increased in FLT mice ( P < 0.05). Finally, many of the genes responsible for scavenging reactive oxygen species were upregulated after flight. These data indicate that exposure to the spaceflight environment can increase anti-inflammatory mechanisms and change the ex vivo response to LPS, a bacterial product associated with septic shock and a prominent Th1 response.

scholarly journals Distinct PKC-mediated posttranscriptional events set cytokine production kinetics in CD8+ T cells

2017 ◽  
Vol 114 (36) ◽  
pp. 9677-9682 ◽  
Author(s):  
Fiamma Salerno ◽  
Nahuel A. Paolini ◽  
Regina Stark ◽  
Marieke von Lindern ◽  
Monika C. Wolkers
Keyword(s):  
T Cells ◽  
Mrna Stability ◽  
Cytokine Production ◽  
De Novo ◽  
Translation Efficiency ◽  
Mrna Stabilization ◽  
Relative Contribution ◽  
Production Kinetics ◽  
Tnf Α ◽  
Ifn Γ

Effective T cell responses against invading pathogens require the concerted production of three key cytokines: TNF-α, IFN-γ, and IL-2. The cytokines functionally synergize, but their production kinetics widely differ. How the differential timing of expression is regulated remains, however, poorly understood. We compared the relative contribution of transcription, mRNA stability, and translation efficiency on cytokine production in murine effector and memory CD8+ T cells. We show that the immediate and ample production of TNF-α is primarily mediated by translation of preformed mRNA through protein kinase C (PKC)-induced recruitment of mRNA to polyribosomes. Also, the initial production of IFN-γ uses translation of preformed mRNA. However, the magnitude and subsequent expression of IFN-γ, and of IL-2, depends on calcium-induced de novo transcription and PKC-dependent mRNA stabilization. In conclusion, PKC signaling modulates translation efficiency and mRNA stability in a transcript-specific manner. These cytokine-specific regulatory mechanisms guarantee that T cells produce ample amounts of cytokines shortly upon activation and for a limited time.

Clinical significance of cytokine markers in children with different courses of community-acquired pneumonia

2020 ◽  
Vol 15 (5) ◽  
pp. 18-23
Author(s):  
G.P. Evseeva ◽  
◽  
G.N. Kholodok ◽  
S.V. Pichugina ◽  
S.V. Suprun ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Interleukin 1 ◽  
Interferon Γ ◽  
Peripheral Blood Lymphocytes ◽  
Community Acquired Pneumonia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interleukin 17 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tnf Α ◽  
Ifn Γ

Principles of the diagnosis and treatment of community-acquired pneumonia (CAP) in children were developed and clearly formulated long ago. Nevertheless, clinicians often encounter the problem of pulmonary and pleural complications of CAP, which is challenging in terms of the choice of initial therapy, since the first symptoms of uncomplicated and complicated pneumonia are often similar. Therefore, the search for early markers of complicated CAP in children is highly important. Objective. To assess prognostic values of spontaneous and mitogen-induced cytokine production in children with CAP. Patients and methods. We have performed comprehensive examination of 108 children with CAP. Eighty-four of them had uncomplicated CAP, whereas 24 children had CAP complicated by pleurisy. We measured spontaneous and induced production of the following cytokines upon patient admission to hospital: interleukin-1 (IL-1), interleukin-17 (IL-17), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1). To measure induced cytokine production, we stimulated peripheral blood lymphocytes by S. рneumonае (serotype 7, 11; strains 7C and 11AD). The level of cytokines was evaluated using the enzyme-linked immunosorbent assay (Vektor-BEST, Novosibirsk, Russia). Results. We found that in children with uncomplicated CAP, induction of immunocompetent blood cells (IBCs) led to increased secretion of first-generation cytokines, including IL-1, TNF-α, and IFN-γ, whereas IBCs of patients with complicated CAP primarily produced second-generation cytokines, including VEGF, МРС-1, and IL-17. Conclusion. The observed differences in spontaneous and mitogen-induced cytokine production between children with and without CAP complications suggest that these parameters can be considered as promising prognostic markers for complicated CAP in children. The proposed method can be used in pediatric practice to predict the development of complications in children with CAP. Key words: children, community-acquired pneumonia, cytokines

scholarly journals Differential Modulation of Human Innate Lymphoid Cell (ILC) Subsets by IL-10 and TGF-β

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sandra Bonne-Année ◽  
Mabel C. Bush ◽  
Thomas B. Nutman
Keyword(s):  
Lymphoid Cell ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Low Frequency ◽  
Surface Expression ◽  
Multiparameter Flow Cytometry ◽  
Innate Lymphoid Cell ◽  
Low Frequencies ◽  
Immunoregulatory Cytokines ◽  
Ifn Γ

Abstract Using multiparameter flow cytometry human innate lymphoid cell (ILC) subsets can be detected in the circulation, in relatively low frequencies. Despite the low frequency of ILCs in circulation, ex vivo experiments have demonstrated that these ILCs release extremely large per cell quantities of signature ILC cytokines following activation. To determine how activated ILC cytokine production is regulated, ILC subsets were activated in the presence or absence of the immunoregulatory cytokines IL-10 and TGF-β. An examination of circulating ILC subsets revealed surface expression of IL-10Rα and mRNA expression of both IL-10Rα and TGF-βR1 for all ILC subsets. Stimulated ILC1 production of IFN-γ was decreased by TGF-β and not IL-10. Interestingly, ILC2s stimulated in the presence of IL-10 had a marked reduction in cytokine production of IL-5 and IL-13 while TGF-β had no effect on ILC2 cytokine production. Ex vivo activated ILC1 and ILC2 subsets were also found to be a source of the immunoregulatory cytokine IL-10, raising the potential for ILC-mediated regulation of immune cells. These findings demonstrate the differential effects of immunoregulatory cytokines IL-10 and TGF-β on activated ILC1 and ILC2 populations ex vivo.

Sign in / Sign up

Export Citation Format

Share Document