PMID- 31969878 OWN - NLM STAT- MEDLINE DCOM- 20201102 LR - 20201102 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 10 DP - 2019 TI - Helicobacter pylori Dampens HLA-II Expression on Macrophages via the Up-Regulation of miRNAs Targeting CIITA. PG - 2923 LID - 10.3389/fimmu.2019.02923 [doi] LID - 2923 AB - Macrophages have a major role in infectious and inflammatory diseases, and the available data suggest that Helicobacter pylori persistence can be explained in part by the failure of the bacterium to be killed by professional phagocytes. Macrophages are cells ready to kill the engulfed pathogen, through oxygen-dependent and -independent mechanisms; however, their killing potential can be further augmented by the intervention of T helper (Th) cells upon the specific recognition of human leukocyte antigen (HLA)-II-peptide complexes on the surface of the phagocytic cells. As it pertains to H. pylori, the bacterium is engulfed by macrophages, but it interferes with the phagosome maturation process leading to phagosomes with an altered degradative capacity, and to megasomes, wherein H. pylori resists killing. We recently showed that macrophages infected with H. pylori strongly reduce the expression of HLA-II molecules on the plasma membrane and this compromises the bacterial antigen presentation to Th lymphocytes. In this work, we demonstrate that H. pylori hampers HLA-II expression in macrophages, activated or non-activated by IFN-gamma, by down-regulating the expression of the class II major histocompatibility complex transactivator (CIITA), the "master control factor" for the expression of HLA class II genes. We provided evidence that this effect relies on the up-regulation of let-7f-5p, let-7i-5p, miR-146b-5p, and -185-5p targeting CIITA. MiRNA expression analysis performed on biopsies from H. pylori-infected patients confirmed the up-regulation of let-7i-5p, miR-146b-5p, and -185-5p in gastritis, in pre-invasive lesions, and in gastric cancer. Taken together, our results suggest that specific miRNAs may be directly involved in the H. pylori infection persistence and may contribute to confer the risk of developing gastric neoplasia in infected patients. CI - Copyright (c) 2020 Codolo, Toffoletto, Chemello, Coletta, Soler Teixidor, Battaggia, Munari, Fassan, Cagnin and de Bernard. FAU - Codolo, Gaia AU - Codolo G AD - Department of Biology, University of Padua, Padua, Italy. FAU - Toffoletto, Marta AU - Toffoletto M AD - Department of Biology, University of Padua, Padua, Italy. FAU - Chemello, Francesco AU - Chemello F AD - Department of Biology, University of Padua, Padua, Italy. AD - CRIBI Biotechnology Center, University of Padua, Padua, Italy. FAU - Coletta, Sara AU - Coletta S AD - Department of Biology, University of Padua, Padua, Italy. FAU - Soler Teixidor, Gemma AU - Soler Teixidor G AD - Department of Biology, University of Padua, Padua, Italy. FAU - Battaggia, Greta AU - Battaggia G AD - Department of Biology, University of Padua, Padua, Italy. FAU - Munari, Giada AU - Munari G AD - Istituto Oncologico Veneto (IRCCS), Padua, Italy. FAU - Fassan, Matteo AU - Fassan M AD - Department of Medicine, University of Padua, Padua, Italy. FAU - Cagnin, Stefano AU - Cagnin S AD - Department of Biology, University of Padua, Padua, Italy. AD - CRIBI Biotechnology Center, University of Padua, Padua, Italy. AD - CIR-Myo Myology Center, University of Padua, Padua, Italy. FAU - de Bernard, Marina AU - de Bernard M AD - Department of Biology, University of Padua, Padua, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200108 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (HLA Antigens) RN - 0 (MHC class II transactivator protein) RN - 0 (MicroRNAs) RN - 0 (Nuclear Proteins) RN - 0 (Trans-Activators) SB - IM MH - Aged MH - Cell Line, Tumor MH - Cells, Cultured MH - Female MH - Gene Expression Profiling/methods MH - HLA Antigens/*immunology MH - Helicobacter Infections/*immunology MH - Helicobacter pylori/*immunology MH - Humans MH - Macrophages/*immunology MH - Male MH - MicroRNAs/*immunology MH - Middle Aged MH - Nuclear Proteins/*immunology MH - Stomach Neoplasms/immunology MH - Trans-Activators/*immunology MH - Up-Regulation/*immunology PMC - PMC6960189 OTO - NOTNLM OT - Helicobacter pylori OT - antigen presentation OT - gastric cancer OT - macrophages OT - miRNA EDAT- 2020/01/24 06:00 MHDA- 2020/11/03 06:00 PMCR- 2019/01/01 CRDT- 2020/01/24 06:00 PHST- 2019/06/13 00:00 [received] PHST- 2019/11/28 00:00 [accepted] PHST- 2020/01/24 06:00 [entrez] PHST- 2020/01/24 06:00 [pubmed] PHST- 2020/11/03 06:00 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2019.02923 [doi] PST - epublish SO - Front Immunol. 2020 Jan 8;10:2923. doi: 10.3389/fimmu.2019.02923. eCollection 2019.