Virulence comparison of human and poultry Campylobacter jejuni isolates in a mouse model

2017 ◽  
Vol 5 (10) ◽  
Author(s):  
Darinka Vučković ◽  
Maja Šikić Pogačar ◽  
Peter Raspor ◽  
Maja Abram ◽  
Sonja Smole Možina ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Mouse Liver ◽  
Virulence Genes ◽  
Cytokine Production ◽  
Host Responses ◽  
Human Origin ◽  
Tnf Α ◽  
Food Isolate ◽  
Ifn Γ ◽  
Food Model

 ABSTRACTObjective: Research into Campylobacter jejuni pathogenesis and host responses to C. jejuni infection is needed in the fight against human campylobacteriosis.Methods: We established intravenous infections of BALB/c mice with either a C. jejuni food isolate or C. jejuni of human origin. Further we include PCR to demonstrate the presence and stability of the putative virulence genes cadF, virbB11, cdtB, cdtC, ceuE in C. jejuni isolates and we examined cytokine production of IL-6, IL-12, TNF-α, IFN-γ, IL-10 in the livers of these infected mice.Results: We confirm here the presence of the cadF, cdtB, cdtC and ceuE genes in a food and a clinical C. jejuni isolate, with no sequence changes after the C. jejuni sub-culturing in a food model and when recovered from mouse liver after infection. Both of these C. jejuni isolates persisted in the mouse livers and activated comparable cytokine patterns for IL-12, TNF-α, IFN-γ and IL-10, with down-regulation of IL-6.Conclusions: These data show the comparability of these C. jejuni food and clinical isolates in terms of the prevalence and stability of their putative virulence genes and the outcome of disease during systemic murine campylobacteriosis.

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 Cytokine production by blood mononuclear cells from in-patients with anorexia nervosa

2002 ◽  
Vol 88 (2) ◽  
pp. 183-188 ◽  
Author(s):  
Esther Nova ◽  
Sonia Gómez-Martínez ◽  
Gonzalo Morandé ◽  
Ascensión Marcos
Keyword(s):  
Anorexia Nervosa ◽  
Immune Function ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Protein Energy Malnutrition ◽  
Control Group ◽  
Control Subjects ◽  
Tnf Α ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

Although protein–energy malnutrition is a common cause of immunodeficiency, the immune function in underweight anorexia nervosa (AN) patients usually seems to be better preserved than would be expected. However, a deranged cytokine production and its consequences are currently being investigated in these patients. This study was aimed at measuring, over time, the capacity of peripheral blood mononuclear cells (PBMC) from AN in-patients to produce several cytokines involved in the regulation of immune responses. The in vitro production of interferon (IFN)-γ, interleukin (IL)-2, tumour necrosis factor (TNF)-α, IL-6 and IL-1β by phytohaemagglutinin-stimulated PBMC were assessed on forty female adolescents with AN. These measures were carried out twice, upon hospital admission and at discharge, which occurred on average after 1 month. Thirty-five control subjects were also studied. Cytokines were measured by ELISA kits. The production of TNF-α and IL-6 was lower and production of IL-1β higher in AN patients than in the control group at both time points of assessment. Refeeding for 1 month was not enough time to reverse these differences and patients still had a low body weight at discharge. IFN-γ production was lower in the patients than in control subjects only at discharge and no differences were found in IL-2 production between both groups. The results suggest that a mechanism involving modifications in the secretion pattern of proinflammatory cytokines could explain some immune function findings in underweight AN patients.

scholarly journals Novel Genetic Regulation of  T Helper 1 (Th1)/Th2 Cytokine Production and Encephalitogenicity in Inbred Mouse Strains

1997 ◽  
Vol 185 (3) ◽  
pp. 439-452 ◽  
Author(s):  
Irina M. Conboy ◽  
Rosemarie H. DeKruyff ◽  
Keri M. Tate ◽  
Zhu A. Cao ◽  
Tom A. Moore ◽  
...  
Keyword(s):  
T Helper Cells ◽  
Cytokine Production ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Th1 Cells ◽  
Inbred Mouse Strains ◽  
T Helper ◽  
Th2 Cytokine ◽  
Tnf Α ◽  
Ifn Γ

Development of T helper cell (Th)1 or Th2 cytokine responses is essential for effector and regulatory functions of T helper cells. We have compared cytokine profiles of myelin basic protein (MBP) Ac1-16 peptide-specific T helper cells from inbred mouse strains expressing identical k haplotype-derived MHC class II molecules B10.A and B10.BR. B10.BR T cell lines (TCL) produced Th1 cytokines (including high levels of TNF-α) and induced experimental autoimmune encephalomyelitis after adoptive transfer. In contrast, B10.A TCL produced Th2 cytokines (including low levels of TNF-α) and were poorly encephalitogenic. The contributions of the genetic origin of the T cells and the APC were explored. Serial restimulations of the B10.BR TCL with B10.A or (B10.A × B10.BR) F1 splenic antigen presenting cells (APC) during the establishment of TCL markedly reduced both Th1 cytokine production and encephalitogenicity. In addition, a single restimulation with B10.A splenic APC reduced IFN-γ and TNF-α production by established Th1 MBP-specific Ak-restricted B10.BR TCL and by a Th1 KLH-specific, Ek-restricted B10.BR T cell clone. These studies suggest that B10.A and B10.BR APC differ in their ability to stimulate IFN-γ and TNF-α production by mature Th1 cells and also influence their Th1/Th2 commitment in vivo. The nature of the downregulatory activity of B10.A APC on IFN-γ and TNF-α production was explored. 2-hour supernatants from antigen-activated B10.A APC/TCL cultures or from B10.A APC activated by LPS had the same inhibitory effects on IFN-γ and TNF-α production by B10.BR TCL. The downregulatory effects of B10.A APC are independent of TNF-α, IL-4, IL-10, IL-12p40, IFN-γ, IL-13, TGF-β, and PGE2. Thus, genetic difference(s) between B10.A and B10.BR APC appear(s) to control the production or activity of a novel soluble cytokine regulatory factor that influences Th1/Th2 commitment and controls production of IFN-γ and TNF-α by mature Th1 cells.

scholarly journals Differential Regulation of DAP12 and Molecules Associated with DAP12 during Host Responses to Mycobacterial Infection

2004 ◽  
Vol 72 (5) ◽  
pp. 2477-2483 ◽  
Author(s):  
Naoko Aoki ◽  
Anna Zganiacz ◽  
Peter Margetts ◽  
Zhou Xing
Keyword(s):  
Mycobacterial Infection ◽  
Host Responses ◽  
Necrosis Factor Alpha ◽  
Lung Macrophage ◽  
Tnf Α ◽  
Kinetic Expression ◽  
Ifn Γ

ABSTRACT DAP12 and its associating molecules MDL-1, TREM-1, and TREM-2 are the recently identified immune regulatory molecules, expressed primarily on myeloid cells including monocytes/macrophages, dendritic cells, NK cells, and neutrophils. However, little is known about the regulation of their expression during host antimicrobial responses. We have investigated the effect of pulmonary mycobacterial infection and type 1 cytokines on the expression of these molecules both in vivo and in vitro. While DAP12 was constitutively expressed at high levels in the lungs, the MDL-1, TREM-1, and TREM-2 molecules were inducible during mycobacterial infection. Their kinetic expression was correlated with that of the type 1 cytokines tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ). In primary lung macrophage cultures, high constitutive levels of DAP12 and TREM-2 were not modulated by mycobacterial or type 1 cytokine exposure. In contrast, expression of both MDL-1 and TREM-1 was markedly induced by mycobacterial infection and such induction was inhibited by concurrent exposure to IFN-γ. On mycobacterial infection of TNF-α−/− and IFN-γ−/− mice in vivo or their lung macrophages in vitro, TNF-α was found to be critical for mycobacterially induced MDL-1, but not TREM-1, expression whereas IFN-γ negatively regulated mycobacterially induced MDL-1 and TREM-1 expression. Our findings thus suggest that DAP12 and its associating molecules are differentially regulated by mycobacterial infection and type 1 cytokines and that MDL-1- and TREM-1-triggered DAP12 signaling may play an important role in antimicrobial type 1 immunity.

scholarly journals Hemozoin Differentially Regulates Proinflammatory Cytokine Production in Human Immunodeficiency Virus-Seropositive and -Seronegative Women with Placental Malaria

2004 ◽  
Vol 72 (12) ◽  
pp. 7022-7029 ◽  
Author(s):  
Julie M. Moore ◽  
Sujittra Chaisavaneeyakorn ◽  
Douglas J. Perkins ◽  
Caroline Othoro ◽  
Juliana Otieno ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Function ◽  
Cytokine Production ◽  
Placental Malaria ◽  
High Density ◽  
Increased Risk ◽  
Tnf Α ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
The Impact

ABSTRACT Pregnant women are at an increased risk for malarial infection. Plasmodium falciparum accumulates in the placenta and is associated with dysregulated immune function and poor birth outcomes. Malarial pigment (hemozoin) also accumulates in the placenta and may modulate local immune function. In this study, the impact of hemozoin on cytokine production by intervillous blood mononuclear cells from malaria-infected placentas was investigated. There was a dose-dependent, suppressive effect of hemozoin on production of gamma interferon (IFN-γ), with less of an effect on tumor necrosis factor alpha (TNF-α) and interleukin-10, in human immunodeficiency virus-seronegative (HIV−) women. In contrast, IFN-γ and TNF-α production tended to increase in HIV-seropositive women with increasing hemozoin levels. Production patterns of cytokines, especially IFN-γ in HIV− women, followed different trends as a function of parasite density and hemozoin level. The findings suggest that the influences of hemozoin accumulation and high-density parasitemia on placental cytokine production are not equivalent and may involve different mechanisms, all of which may operate differently in the context of HIV infection. Cytokine production dysregulated by accumulation of hemozoin or high-density parasitemia may induce pathology and impair protective immunity in HIV-infected and -uninfected women.

scholarly journals Campylobacter jejuni Induces Maturation and Cytokine Production in Human Dendritic Cells

2006 ◽  
Vol 74 (5) ◽  
pp. 2697-2705 ◽  
Author(s):  
Lan Hu ◽  
Mechelle D. Bray ◽  
Manuel Osorio ◽  
Dennis J. Kopecko
Keyword(s):  
Dendritic Cells ◽  
Campylobacter Jejuni ◽  
Cytokine Production ◽  
Diarrheal Disease ◽  
Inflammatory Responses ◽  
Bacterial Invasion ◽  
Microbial Infection ◽  
Necrosis Factor Alpha ◽  
Adaptive Immune ◽  
Tnf Α

ABSTRACT Campylobacter jejuni is a leading bacterial cause of human diarrheal disease in both developed and developing nations. Colonic mucosal invasion and the resulting host inflammatory responses are thought to be the key contributing factors to the dysenteric form of this disease. Dendritic cells (DCs) play an important role in both the innate and adaptive immune responses to microbial infection. In this study, the interaction between human monocyte-derived dendritic cells and C. jejuni was studied. We found that C. jejuni was readily internalized by DCs over a 2-h period. However, after a prolonged infection period (24 or 48 h) with C. jejuni, only a few viable bacteria remained intracellularly. Minimal cytotoxicity of C. jejuni to dendritic cells was observed. C. jejuni induced the maturation of dendritic cells over 24 h, as indicated by up-regulation of cell surface marker proteins CD40, CD80, and CD86. In addition, Campylobacter-infected DCs triggered activation of NF-κB and significantly stimulated production of interleukin-1β (IL-1β), IL-6, IL-8, IL-10, IL-12, gamma interferon, and tumor necrosis factor alpha (TNF-α) compared to uninfected DCs. Active bacterial invasion of DCs was not necessary for the induction of these cytokines, as heat-killed C. jejuni stimulated similar levels of cytokine production as live bacteria. Purified lipooligosaccharide of C. jejuni appears to be the major stimulant for the increased production of cytokines by DCs. Taken together, these data indicate that during infection, Campylobacter triggers an innate inflammatory response through increased production of IL-1β, IL-6, IL-8, and TNF-α and initiates a Th1-polarized adaptive immune response as predicted from the high level of production of IL-12.

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 A Cross-Protective Vaccine Against 4b and 1/2b Listeria monocytogenes

2020 ◽  
Vol 11 ◽  
Author(s):  
Fanzeng Meng ◽  
Tengfei Zhu ◽  
Hao Yao ◽  
Zhiting Ling ◽  
Youwei Feng ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Vaccine Strain ◽  
Virulence Genes ◽  
Control Group ◽  
Listeriolysin O ◽  
Protective Efficiency ◽  
Zoonotic Pathogen ◽  
Tnf Α ◽  
Boost Immunization ◽  
Ifn Γ

Listeria monocytogenes (Lm) is a foodborne zoonotic pathogen that causes listeriosis with a mortality rate of 20–30%. Serovar 4b and 1/2b isolates account for most of listeriosis outbreaks, however, no listeriosis vaccine is available for either prophylactic or therapeutic use. Here, we developed a triple-virulence-genes deletion vaccine strain, and evaluated its safety, immunogenicity, and cross-protective efficiency. The virulence of NTSNΔactA/plcB/orfX was reduced 794-folds compared with the parental strain. Additionally, it was completely eliminated in mice at day 7 post infection and no obvious pathological changes were observed in the organs of mice after prime-boost immunization for 23 days. These results proved that the safety of the Lm vaccine strain remarkably increased. More importantly, the NTSNΔactA/plcB/orfX strain stimulated higher anti-Listeriolysin O (LLO) antibodies, induced significantly higher expression of IFN-γ, TNF-α, IL-17, and IL-6 than the control group, and afforded 100% protection against serovar 4b and 1/2b challenges. Taken together, our research demonstrates that the triple-genes-deletion vaccine has high safety, can elicit strong Th1 type immune response, and affords efficient cross-protection against two serovar Lm strains. It is a promising vaccine for prevention of listeriosis.

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