Ex Vivo Innate Immune Cytokine Signature of Enhanced Risk of Relapsing Brucellosis

Feldman, Kristyn E.; Loriaux, Paul; Saito, Mayuko; Tuero, Iskra; Villaverde, Homarh; Siva, Tenaya; Gotuzzo, Eduardo; Gilman, Robert H.; Hoffmann, Alexander; Vinetz, Joseph M.

doi:10.1371/journal.pntd.0002424

Cited by 7 publications

(7 citation statements)

References 33 publications

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“…They concluded that acute and relapse patients were largely identical by their cytokine gene expression profiles, however, there was a strong cytokine secretion that accurately discriminates acute from relapse patients which may allow for better follow up care of brucellosis patients through improved identification of patients at risk of relapse. We have found several similar results to those of Feldman et al, [28] particularly in the case of TNF-a levels, in which they observed higher expression after LPS stimulation compared with both acute brucellosis and control donors. They also observed increased IFN-g expression after HKBM stimulation in relapse patients and concluded that relapse of brucellosis in patients can induce the expression of cytokines necessary to mount a Th1 response.…”

Section: Discussionsupporting

confidence: 90%

“…Interestingly, during relapse of brucellosis, we observed a significant decrease in inflammatory cytokines, except for TNF-a and IL-15, in the systemic circulation. Recently, Feldman et al [28] performed an ex vivo study to measure the expression and secretion of several inflammatory cytokines in peripheral blood mononuclear cells after stimulation with LPS or heat-killed B. melitensis (HKBM). They concluded that acute and relapse patients were largely identical by their cytokine gene expression profiles, however, there was a strong cytokine secretion that accurately discriminates acute from relapse patients which may allow for better follow up care of brucellosis patients through improved identification of patients at risk of relapse.…”

Section: Discussionmentioning

confidence: 99%

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Mystery of Immune Response in Relapsed Brucellosis: Immunophenotyping and Multiple Cytokine Analysis

Kayhan¹,

Kayabaş²,

Kölgelier³

et al. 2016

mjima

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Introduction: Brucella spp. are intracellular bacteria that may cause acute, subacute and chronic infections. Despite optimum antibiotic treatment, relapse of brucellosis occurs in some patients. There is less amount of knowledge about immune response in relapse of brucellosis. Materials and Methods: Twenty patients with acute brucellosis, 16 patients with relapsed brucellosis and as a control group 20 healthy volunteers were enrolled in this study to explore the immune response variation during relapse of brucellosis. The distribution of peripheral blood mononuclear cells was investigated by flow cytometry and level of various cytokines involved in inflammatory and anti-inflammatory response were measured by enzyme-linked immunosorbent assay in serum samples. Results: The most prominent data in phenotyping examination was the significant reduction (1.45 times) in the percentage of activated T cell (CD3 + human leukocyte antigen-DR +) population in the relapse group in comparison to the acute brucellosis group. However, percentage of activated T cell population in the relapse group was 2.59 times higher than in healthy controls (p<0.01). We observed a significant reduction in inflammatory cytokines interleukin (IL)-6, IL-18, interferon-g and IL-17 in relapsed patients in comparison to patients with acute brucellosis. While there was no significant difference in IL-15 and tumor necrosis factor-a levels between relapse and acute brucellosis groups, the levels of these two cytokines were significantly higher in the relapse group than in healthy subjects. In case of anti-inflammatory cytokines, while IL-4 levels increased significantly only in relapse group, IL-10 levels increased both in acute and relapse brucellosis group in comparison to healthy controls. Interestingly, we observed 2.87 times elevation in IL-4 levels in the relapse group in comparison to acute brucellosis (p<0.01). Similarly; IL-10 levels increased 2.09 times in patients with relapsed brucellosis patients in comparison to acute brucellosis (p<0.01). Conclusion: Elevation of regulatory cytokines in systemic immune system and reduction of activated T cell frequency occur during the relapse of brucellosis. These results may contribute to understanding the immunopathology in the systemic circulation during relapse of brucellosis.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Mystery of Immune Response in Relapsed Brucellosis: Immunophenotyping and Multiple Cytokine Analysis

Kayhan¹,

Kayabaş²,

Kölgelier³

et al. 2016

mjima

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“…While most patients recover with a standard antibiotic treatment, 5-40z of patients suffer from relapsing brucellosis (21). Acute and relapse patients demonstrated consistently elevated cytokine gene expression and secretion levels compared to those of controls.…”

Section: Discussionmentioning

confidence: 99%

“…Acute and relapse patients demonstrated consistently elevated cytokine gene expression and secretion levels compared to those of controls. Notably, this includes the basal secretion of IL-6, IL-8, IL-1b, IL-2, and TNF-a in response to lipopolysaccharides and heat-killed B. melitensis (HKBM), and IFN-g secretion in response to HKBM (21). In one animal study, MIF was up-regulated in infected rams (22).…”

Section: Discussionmentioning

confidence: 99%

The IL4-VNTR P1 Allele, IL4-VNTR P2P2 Genotype, and IL4-VNTR_IL6-174CG P2P1-GG Genotype Are Associated with an Increased Risk of Brucellosis

et al. 2017

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SUMMARY:In this study, associations between IL-4, IL-6, and macrophage migration inhibitory factor (MIF ) polymorphisms and susceptibility to brucellosis were investigated. Consecutive adult patients with no known treatment against brucellosis and who did not have any other autoimmune and/or chronic disorders, were included in this study (n ＝ 120, Group I). Age and sex-matched controls who had no other autoimmune and/or chronic disorders were also included (n ＝ 120, healthy volunteers, Group II). The IL4_P2P2 genotype, IL4_P1 allele, and IL4_variable number of tandem repeats (VNTR)_IL6-174CG compound genotype were found to be more frequent in the patient group than in control subjects. There were significant differences between the patients and controls with respect to the frequencies of the IL4_P2P2 genotype (77.5z versus 87.5z; p ＝ 0.001; OR, 0.36; 95z confidence interval [CI], 0.21-0.62) and the IL4_P1 allele (12.1z versus 6.7z; p ＝ 0.030; OR, 0.92; CI,

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“…Infected macrophages produce critical cytokines such as TNF-α, enhancing the bactericidal activity of phagocytes, and IL-12, driving the Th1 immune response. IL-12 induces the production of IFN-γ from CD4 + , CD8 + , and γδ T lymphocytes, resulting in the Th1 immune response and bactericidal activity of macrophages, which in turn lead to the prevention of the intracellular survival of Brucella (17,24). In addition, cytotoxic activity of the CD8 + and T cells are significant for killing the infected macrophages (25).…”

Section: 12cell-mediated Immunitymentioning

confidence: 99%

Vaccines and Vaccine Candidates against Brucellosis

Mansoori¹,

Pourmand²

2016

IEM

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Brucella is a facultative intracellular pathogen, and brucellosis is commonest zoonotic disease worldwide. Brucella species, isolated from domestic animals, are important pathogen for humans. Annually, more than 500,000 new cases of brucellosis are reported, and this figure is an underestimate due to extended under-reporting cases in several endemic countries. Brucella has a variety of virulence mechanisms that prevent detection and activation of innate immunity, but protection against intracellular pathogen is represented by cell-mediated immunity. As yet, much research has been performed to develop a safe Brucella vaccine to control the disease in human and animals. Despite the availability of several live attenuated vaccine for animals, currently, no effective human vaccine is available. Moreover, due to the potential use of Brucella in bioterrorism or biowarfare, development of an effective vaccine against brucellosis for human use is necessary. In this paper, we aimed to review and discuss the efforts of researchers to develop vaccines against Brucellosis.

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Ex Vivo Innate Immune Cytokine Signature of Enhanced Risk of Relapsing Brucellosis

Cited by 7 publications

References 33 publications

Mystery of Immune Response in Relapsed Brucellosis: Immunophenotyping and Multiple Cytokine Analysis

Mystery of Immune Response in Relapsed Brucellosis: Immunophenotyping and Multiple Cytokine Analysis

The IL4-VNTR P1 Allele, IL4-VNTR P2P2 Genotype, and IL4-VNTR_IL6-174CG P2P1-GG Genotype Are Associated with an Increased Risk of Brucellosis

Vaccines and Vaccine Candidates against Brucellosis

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