Tumor Necrosis Factor-α, Interleukins-12(p40), 6, and 10 levels in cerebrospinal fluid and outcome prediction in Ossimi sheep with encephalitic listeriosis

Abdlla, Ossama A.; El‐Boshy, Mohamed; Reisha, Engy F.; Gadlla, Hossam A.; El-Khodery, Sabry

doi:10.1016/j.cyto.2015.03.004

Cited by 7 publications

(9 citation statements)

References 39 publications

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“…We also detected high titres of anti-GAPDH 1-22 antibodies in sera of GNP-GAPDH 1-22 -vaccinated mothers (GNP-GAPDH 1-22 + LM WT ) (Table 4 ), which is another indicator of vaccine efficiency in listeriosis [ 10 , 39 ]. Microglia of P4 neonates born to NV and LM WT -infected mothers presented high levels of IL-6, IL-10 and TNF-α and lacked production of IL-12p40 (Table 4 ); a Th2 pattern similar to the cytokine profile reported in meningitis and encephalitic cases of listeriosis [ 4 , 33 , 35 ]. We also detected low titres of anti-GAPDH 1-22 antibodies in sera of NV mothers and infected with LM WT or LM ∆ActA , suggesting low induction of specific immune responses (Table 4 ).…”

Section: Resultsmentioning

confidence: 70%

“…Patients with neonatal listeriosis presented with high titres of anti-GAPDH 1-22 and undetectable anti-LLO 189-201 antibodies, normal percentages of monocytes and CD8 + T cells, and higher numbers of mature and immature granulocytes as a result of bacterial infection (Figure 1B ). A predominant Th2 cytokine profile with low Th1-Th17/IL-6 ratios, is also a biomarker of poor prognosis in adult listeriosis because it favours bacterial growth [ 1 , 3 , 4 , 9 ]. We observed that neonatal listeriosis patients also presented low TNF-α/IL-6 ratios, indicating predominant Th2 immune responses (Figure 1C ).…”

Section: Resultsmentioning

confidence: 99%

“…Cerebral listeriosis caused by the human pathogen Listeria monocytogenes (LM) constitutes a severe disease in infants and elderly people, with a mortality rate of 30% [ 1 ]. LM targets the central nervous system (CNS) and foetus, and the most common listeriosis-related diseases are meningitis, meningoencephalitis, brain abscesses, foetal malformations and septicaemia [ 2 – 4 ]. Since 2008, the cases of listeriosis have increased in the European Union, but especially in Spain, where listeriosis cases reported between 2008 and 2014 are 1.15 cases per 100,000 inhabitants [ 5 – 7 ].…”

Section: Introductionmentioning

confidence: 99%

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GNP-GAPDH1-22 nanovaccines prevent neonatal listeriosis by blocking microglial apoptosis and bacterial dissemination

et al. 2017

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Clinical cases of neonatal listeriosis are associated with brain disease and fetal loss due to complications in early or late pregnancy, which suggests that microglial function is altered. This is believed to be the first study to link microglial apoptosis with neonatal listeriosis and listeriosis-associated brain disease, and to propose a new nanovaccine formulation that reverses all effects of listeriosis and confers Listeria monocytogenes (LM)-specific immunity. We examined clinical cases of neonatal listeriosis in 2013–2015 and defined two useful prognostic immune biomarkers to design listeriosis vaccines: high anti-GAPDH1-22 titres and tumor necrosis factor (TNF)/interleukin (IL)-6 ratios. Therefore, we developed a nanovaccine with gold glyco-nanoparticles conjugated to LM peptide 1-22 of GAPDH (Lmo2459), GNP-GAPDH1-22 nanovaccinesformulated with a pro-inflammatory Toll-like receptor 2/4-targeted adjuvant. Neonates born to non-vaccinated pregnant mice with listeriosis, showed brain and vascular diseases and significant microglial dysfunction by induction of TNF-α-mediated apoptosis. This programmed TNF-mediated suicide explains LM dissemination in brains and livers and blocks production of early pro-inflammatory cytokines such as IL-1β and interferon-α/β. In contrast, neonates born to GNP-GAPDH1–22-vaccinated mothers before LM infection, did not develop listeriosis or brain diseases and had functional microglia. In nanovaccinated mothers, immune responses shifted towards Th1/IL-12 pro-inflammatory cytokine profiles and high production of anti-GAPDH1–22 antibodies, suggesting good induction of LM-specific memory.

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Section: Resultsmentioning

confidence: 70%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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GNP-GAPDH1-22 nanovaccines prevent neonatal listeriosis by blocking microglial apoptosis and bacterial dissemination

et al. 2017

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“…Listeriosis patients with other co-morbidities presented better Th17 and CD4 + T cell immune responses. High levels of IL-6 were also reported in bacterial meningitis of children and experimental listeriosis (32, 33), suggesting this cytokine plays a relevant role. Moreover, IL-10 high levels were also reported to increase in listeriosis of aged mice with high bacterial loads (28).…”

Section: Discussionmentioning

confidence: 93%

Biomarker Tools to Design Clinical Vaccines Determined from a Study of Annual Listeriosis Incidence in Northern Spain

et al. 2016

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Two regions of northern Spain, Gipuzkoa, and Cantabria present high annual incidence of listeriosis (1.86 and 1.71 cases per 100,000 inhabitants, respectively). We report that the high annual incidences are a consequence of infection with highly virulent Listeria monocytogenes isolates linked to fatal outcomes in elderly patients with cancer. In addition, listeriosis patients with cancer present low IL-17A/IL-6 ratios and significantly reduced levels of anti-GAPDH1–22 antibodies, identified as two novel biomarkers of poor prognosis. Analysis of these biomarkers may aid in reducing the incidence of listeriosis. Moreover, GAPDH1–22-activated monocyte-derived dendritic cells of listeriosis patients with cancer seem useful tools to prepare clinical vaccines as they produce mainly Th1 cytokines.

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“…The results of other animal experiments have indicated that systematic application of IL-12 not only promotes primary tumor regression but may also promote regression of metastatic lesions and exert an antiangiogenic effect. [4][5][6] Dendritic cells (DCs) are good antigen-presenting cells in the body that can effectively induce proliferation and response of resting T cells as well as promote the generation of helper T lymphocytes and cytotoxic T lymphocytes. Dendritic cellbased immunotherapy can aid in the targeted killing of tumor cells without harming normal cells and can therefore be used as a promising cancer treatment method.…”

Section: Introductionmentioning

confidence: 99%

Functional Changes of Dendritic Cells in C6 Glioma-Bearing Rats That Underwent Combined Argon-Helium Cryotherapy and IL-12 Treatment

Cui

et al. 2016

Technol Cancer Res Treat

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Objective: The aim of this study was to explore changes in tumor tissues of glioma-bearing rats that underwent argon-helium cryoablation as well as changes in antitumor immunity before and after combined interleukin 12 treatment. Methods: Two hundred sixty Wistar rats were randomly divided into a blank control group, intravenous injection interleukin-12 group, cryotherapy group, and cryotherapy þ intravenous injection group. C6 glioma cells proliferated in vitro were implanted subcutaneously on the backs of rats to establish C6 glioma-bearing animal models. Each group underwent the corresponding treatments, and morphological changes in tumor tissues were examined using hematoxylin-eosin staining. CD11c staining was examined using immunohistochemistry, and differences in dendritic cells and T-cell subsets before and after treatment were analyzed using flow cytometry. Results: The control group showed no statistical changes in terms of tumor tissue morphology and cellular immunity, cryotherapy group, and cryotherapy þ intravenous injection group, among which the count for the cryotherapy þ intravenous injection group was significantly higher than those of all other groups. In the argon-helium cryotherapy group, tumor cells were damaged and dendritic cell markers were positive. The number of CD11cþ and CD86þ cells increased significantly after the operation as did the cytokine interferon-g level (P < .01), suggesting a shift toward Th1-type immunity. Conclusion: Combined treatment of argon-helium cryoablation and interleukin 12 for gliomas not only effectively injured tumor tissues but also boosted immune function and increased antitumor ability. Therefore, this approach is a promising treatment measure for brain gliomas.

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Tumor Necrosis Factor-α, Interleukins-12(p40), 6, and 10 levels in cerebrospinal fluid and outcome prediction in Ossimi sheep with encephalitic listeriosis

Cited by 7 publications

References 39 publications

GNP-GAPDH1-22 nanovaccines prevent neonatal listeriosis by blocking microglial apoptosis and bacterial dissemination

GNP-GAPDH1-22 nanovaccines prevent neonatal listeriosis by blocking microglial apoptosis and bacterial dissemination

Biomarker Tools to Design Clinical Vaccines Determined from a Study of Annual Listeriosis Incidence in Northern Spain

Functional Changes of Dendritic Cells in C6 Glioma-Bearing Rats That Underwent Combined Argon-Helium Cryotherapy and IL-12 Treatment

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