ABSTRACT
Patients with liver disease are susceptible to infection with Vibrio vulnificus (V. vulnificus), but the specific reasons remain elusive. Through RNA-seq, we found that when mice with alcoholic liver disease (ALD) were infected with V. vulnificus by gavage, compared with the Pair group, the small intestinal genes affecting intestinal permeability were upregulated; and the number of differentially expressed genes related to immune functions (e.g., such as cell chemotaxis, leukocyte differentiation, and neutrophil degranulation) decreased in the liver, spleen, and blood. Further analysis showed that the number of white blood cells decreased in the Pair group, whereas those in the ALD mice did not change significantly. Interestingly, the blood bacterial load in the ALD mice was about 100 times higher than that of the Pair group. After the ALD mice were infected with V. vulnificus, the concentrations of T cell proliferation-promoting cytokines (IL-2, IL-23) decreased. Therefore, unlike the Pair group, ALD mice had weaker immune responses, lower T cell proliferation-promoting cytokines, and higher bacterial loads post-infection, possibly increasing their susceptibility to V. vulnificus infection. These new findings we presented here may help to advance the current understanding of the reasons why patients with liver disease are susceptible to V. vulnificus infection and provides potential targets for further investigation in the context of treatment options for V. vulnificus sepsis in liver disease patient.
Subject(s)
Cytokines/metabolism , Liver Diseases, Alcoholic/immunology , Transcriptome , Vibrio Infections/immunology , Vibrio vulnificus/pathogenicity , Animals , Bacterial Load , Cell Proliferation , Cytokines/genetics , Disease Models, Animal , Female , Gene Expression Profiling , Host-Pathogen Interactions , Liver Diseases, Alcoholic/genetics , Liver Diseases, Alcoholic/metabolism , Lymphocyte Activation , Mice, Inbred C57BL , RNA-Seq , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , T-Lymphocytes/microbiology , Vibrio Infections/genetics , Vibrio Infections/metabolism , Vibrio vulnificus/growth & development , Vibrio vulnificus/immunologyABSTRACT
Diagnosis of the early-invasive oral squamous cell carcinoma (OSCC) can be challenged in biopsies, and immunohistochemistry is commonly used in such settings. A double immunohistochemical staining (DIHC) containing both E-cadherin (E-cad) and podoplanin antibodies were developed and its use in the diagnosis of limited cancer in the early-invasive was evaluated. In this study, the expressions of E-cadherin and podoplanin were checked by the way of DIHC in 214 oral biopsy tissues including normal oral epithelial (NOE), oral epithelial dysplasia (OED), squamous carcinoma in situ (SCIS), and OSCC. Meanwhile, 17 indecisive cases whose original diagnoses were SCIS incidentally suspicious infiltration had been checked. Tumor specimens presented a significant loss of expression of E-cad when compared with normal epithelium. In all NOE and 62.5% ofOED tissues, the expression of E-cad showed positive clearly and strongly in cell membrane, while podoplanin was showed negative.The expression of E-cad was showed positive in 35.6% of SCIS as the expressions of podoplanin became stronger. The expression of E-cad declined obviously and the expression of podoplanin became stronger in the 54.8% of OSCC. The expression of podoplanin was easier to be observed in the same slice due to the decreased expression of E-cad in malignant cell. By the same way, early-invasions were showed clearly in 5 cases of 17 indecisive cases. The decrease of E-cad and the increase of podoplanin had closely relationship with OSCC (P<0.05). The cocktail double staining of E-cad and podoplanin may offer an objective index for the decision of the early-invasive oral squamous cell carcinoma.
