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Mucosal-associated invariant T (MAIT) cells, defined as CD161++TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3+CD161++TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR) iVα7.2+ CD161+ MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4+ T cells and MAIT cells and with CD57 on CD8+ T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2+ MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1.

Figure 1 IL22 induces an ER stress/unfolded protein response transcriptional module in colonic epithelial cells. (A) Heat map demonstrating pathway specific transcript expression in murine colonoids treated with (+IL22, n=3) or without (control, n=3) recombinant IL22. Mouse gene 2.0 ST array platform (affymetrix). (B) GSEA evaluating enrichment of ER stress response transcriptional module in IL22 treated colonoids. A core set of colonic epithelial-specific ER stress genes was defined by analysing significantly differentially expressed (p<0.05 and absolute value of the log2 fold change >±2) transcripts in colonoids treated with tunicamycin (n=3) or medium alone (n=3). (C) Expression of ER stress response transcripts in IL22 treated WT and Il22ra1 −/− colonoids (RNA-seq dataset ERR247358-ERR247389, Pham et al, 2014). 18 (D) Enrichment analysis for ER stress-related functional annotation groups (GO biological processes) in IL22-treated colonoids from dataset ERR247358-ERR247389. (E) Microarray analysis of core ER stress response transcripts in colonoids treated with tunicamycin (n=3), tunicamycin+IL22 (n=3) or untreated (control, n=3). (F) Real-time PCR quantification of ER stress transcripts in colonoids treated with IL22 (n=11), IL17A (n=6) and IL22+IL17A (n=6) and unexposed controls. *P<0.01. (G) Immunoblot and densitometry quantification (H) detecting GRP78 protein expression in colonoids treated with different cytokines. *P<0.026, one tailed t test. ER, endoplasmic reticulum; GO, Gene Ontology; GSEA, Gene Set Enrichment Analysis; IL22, interleukin-22.on July 6, 2020 by guest. Protected by copyright.

Immune exhaustion and senescence of CD8(+) CD161(++) TCR Vα7.2(+) MAIT cells could contribute to diminished innate defence attributes likely facilitating viral persistence and HCV disease progression.

Hepatitis B virus (HBV) infection is a major cause of chronic liver disease that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses represent the key determinants of HBV clearance or persistence. Here, we investigated the role of the early activation marker, CD69 and effector cytokines, granzyme B (GrB) and IFN-γ in the exhaustion of innate-like TCR Vα7.2CD4T cells, in 15 individuals with chronic HBV (CHB) infection where six were HBV DNA and nine were HBV DNA. The percentage of cytokine-producing T cells and MAIT cells were significantly perturbed in HBV patients relative to healthy controls (HCs). The intracellular expression of GrB and IFN-γ was significantly reduced in MAIT cells derived from HBV-infected patients as compared to HCs, and the levels correlated with the percentage and levels [mean fluorescence intensity (MFI)] of CD69 expression. The total expression of CD69 (iMFI) was lower in CHB patients as compared to HCs. The frequency of CD69 cells correlated with the levels of cytokine expression (MFI), particularly in CHB patients as compared to HCs. In summary, the polyfunctionality of peripheral T cells was significantly reduced among CHB patients, especially in the TCR Vα7.2CD4T cells, and the levels of cytokine expression correlated with functional cytokine levels.

The resistance rates of the antibiotics used in primary treatment of H. pylori infections in Malaysia are low, and multi-antibiotic-resistant strains are uncommon. Infections with mixed populations of metronidazole-sensitive and -resistant strains were also observed. However, the high metronidazole MIC values seen among the metronidazole-resistant strains are a cause for concern.

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