Helicobacter suis induces changes in gastric inflammation and acid secretion markers in pigs of different ages

International audienceAbstractGastric mRNA expression of markers for acid secretion and inflammation and presence of gastric ulceration was studied in naturally Helicobacter suis-infected and non-infected 2–3 months old, 6–8 months old and adult pigs. In H. suis-infected 2–3 months old pigs, IL-8 and IL-1β transcript levels were upregulated in the pyloric gland zone, indicating an innate immune response. A similar response was demonstrated in the fundic gland zone of adult pigs, potentially due to a shift of H. suis colonization from the pyloric to the fundic gland zone. A Treg response in combination with decreased expressions of IL-8, IL-17A and IFN-γ was indicated to be present in the H. suis-infected 6–8 months old pigs, which may have contributed to persistence of H. suis. In H. suis-infected adult pigs, a Treg response accompanied by a Th17 response was indicated, which may have played a role in the decreased number of H. suis bacteria in the stomach of this age group. The decreased G-cell mass and upregulated expression of somatostatin indicated decreased acid secretion in H. suis-infected 6–8 months old pigs. In H. suis-infected adult pigs, upregulation of most markers for gastric acid secretion and increased G-cell mass was detected. Presence of severe hyperkeratosis and erosions in the non-glandular part of the stomach were mainly seen in the H. suis-positive groups. These results show that H. suis infection affects the expression of markers for acid secretion and inflammation and indicate that these effects differ depending on the infection phase

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Additional file 8. Overview of important correlations between markers for gastric acid secretion and the number of H. suis bacteria in pigs of different ages. r = Pearson correlation coefficient, calculated using SPSS Statistics 24Ž. A r-value close to 1 indicates a strong, positive correlation, whereas a r-value of -1 indicates a strong, negative correlation. P-values lower than 0.05 are considered to be significant

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Additional file 9. Correlations of altered markers for gastric acid secretion with the number of H. suis bacteria and with the altered markers for inflammation in H. suis -infected pigs of different age groups. r = Pearson correlation coefficient, calculated using SPSS Statistics 24®. A r-value close to 1 indicates a strong, positive correlation, whereas a r-value of −1 indicates a strong, negative correlation. P-values lower than 0.05 are considered to be significant./= no clear correlation, yes = correlation with H. suis colonization rate (see Additional files 6, 8 for the r and p-values)

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Additional file 3. General overview of the average scores of infiltration with inflammatory cells and lymphoid follicle formation in the fundic and pyloric gland zone of pigs of different ages. Gastritis was scored based on infiltration with inflammatory cells/lymphoid follicle formation, with score 0 = absence of infiltration/absence of lymphoid aggregates, 1 = mild infiltration/small number of lymphoid aggregates (n < 5), 2 = moderate infiltration/large number of lymphoid aggregates (n > 5) or presence of 1 organized lymphoid follicle, 3 = marked infiltration/at least 2 organized lymphoid follicles, n = total number of investigated pigs’ stomachs per age group. The data are shown as the average of the administered scores with standard deviation

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Additional file 6. Overview of important correlations between markers for inflammation and the number of H. suis bacteria in pigs of different ages. r = Pearson correlation coefficient, calculated using SPSS Statistics 24®. A r-value close to 1 indicates a strong, positive correlation, whereas a r-value of −1 indicates a strong, negative correlation. A p-value lower than 0.05 is considered to be significant

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Additional file 4. Microscopic visualization of the parietal cells (A), D-cells (B) and G-cells (C–D) in the porcine stomach using immunohistochemistry. (A) H+/K+ ATPase staining of the fundic gland zone of a H. suis-positive adult sow, showing parietal cells (brown). No clear parietal cell loss was detected. Original magnification ×100. (B) Somatostatin staining of the pyloric gland zone of a H. suis-positive adult sow, showing D-cells (brown). Original magnification ×200. (C) Gastrin staining of the pyloric gland zone of a H. suis-positive adult sow, showing G-cells (brown). Original magnification ×200. (D) Gastrin staining of the pyloric gland zone of a H. suis-negative sow, showing G-cells (brown). Original magnification ×200. The number of G-cells in the H. suis-negative sow (D) is lower than observed in the H. suis-positive sow (C)

STAT3-dependent VEGF production from keratinocytes abrogates dendritic cell activation and migration by arsenic: a plausible regional mechanism of immunosuppression in arsenical cancers

[[abstract]]Arsenic remains an important environmental hazard that causes several human cancers. Arsenic-induced Bowen’s disease (As-BD), a skin carcinoma in situ, is the most common arsenical cancer. While great strides have been made in our understanding of arsenic carcinogenesis, how host immunity contributes to this process remains unknown. Patients with As-BD have an impaired contact hypersensitivity response. Although impaired T cell activation has been well-documented in arsenical cancers, how dendritic cell (DC), the key cell regulating innate immunity, regulates the immune response in arsenical cancers remains unclear. Using myeloid derived DC (MDDC) from patients with As-BD and normal controls as well as bone marrow derived DC (BMDC) from mice fed with or without arsenic, we measured the migration of DC. As-BD patients showed an impaired CCL21-mediated MDDC migration in vitro. Arsenic-fed mice had defective DC migration towards popliteal lymph nodes when injected with allogenic BMDCs via foot pad. Using skin from As-BD and normal controls, we found an increased expression of STAT3, a transcriptional factor contributing to impaired DC activation. Arsenic induced STAT3 activation and the production of VEGF in keratinocytes. The increase in VEGF was blocked by inhibiting STAT3 with RNA interference or pharmaceutically with JSI-124. While VEGF by itself minimally induced the expression of CD86 and MHC-II in MDDC, arsenic induced-MDDC activation was abolished by VEGF pretreatment. We concluded that the STAT3-VEGF axis in keratinocytes inhibits DC migration in the microenvironment of As-BD, indicating that cellular interactions play an important role in regulating the disease course of arsenical cancers