Helicobacter pylori Dampens HLA-II Expression on Macrophages via the Up-Regulation of miRNAs Targeting CIITA
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, thro...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02923/full |
| _version_ | 1819111700900610048 |
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| author | Gaia Codolo Marta Toffoletto Francesco Chemello Francesco Chemello Sara Coletta Gemma Soler Teixidor Greta Battaggia Giada Munari Matteo Fassan Stefano Cagnin Stefano Cagnin Stefano Cagnin Marina de Bernard |
| author_facet | Gaia Codolo Marta Toffoletto Francesco Chemello Francesco Chemello Sara Coletta Gemma Soler Teixidor Greta Battaggia Giada Munari Matteo Fassan Stefano Cagnin Stefano Cagnin Stefano Cagnin Marina de Bernard |
| author_sort | Gaia Codolo |
| collection | DOAJ |
| description | 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-γ, 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. |
| first_indexed | 2024-12-22T04:01:47Z |
| format | Article |
| id | doaj.art-08b071b3d65c404b858ba91d3c0e9967 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T04:01:47Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-08b071b3d65c404b858ba91d3c0e99672022-12-21T18:39:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-01-011010.3389/fimmu.2019.02923478325Helicobacter pylori Dampens HLA-II Expression on Macrophages via the Up-Regulation of miRNAs Targeting CIITAGaia Codolo0Marta Toffoletto1Francesco Chemello2Francesco Chemello3Sara Coletta4Gemma Soler Teixidor5Greta Battaggia6Giada Munari7Matteo Fassan8Stefano Cagnin9Stefano Cagnin10Stefano Cagnin11Marina de Bernard12Department of Biology, University of Padua, Padua, ItalyDepartment of Biology, University of Padua, Padua, ItalyDepartment of Biology, University of Padua, Padua, ItalyCRIBI Biotechnology Center, University of Padua, Padua, ItalyDepartment of Biology, University of Padua, Padua, ItalyDepartment of Biology, University of Padua, Padua, ItalyDepartment of Biology, University of Padua, Padua, ItalyIstituto Oncologico Veneto (IRCCS), Padua, ItalyDepartment of Medicine, University of Padua, Padua, ItalyDepartment of Biology, University of Padua, Padua, ItalyCRIBI Biotechnology Center, University of Padua, Padua, ItalyCIR-Myo Myology Center, University of Padua, Padua, ItalyDepartment of Biology, University of Padua, Padua, ItalyMacrophages 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-γ, 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.02923/fullHelicobacter pylorimiRNAmacrophagesantigen presentationgastric cancer |
| spellingShingle | Gaia Codolo Marta Toffoletto Francesco Chemello Francesco Chemello Sara Coletta Gemma Soler Teixidor Greta Battaggia Giada Munari Matteo Fassan Stefano Cagnin Stefano Cagnin Stefano Cagnin Marina de Bernard Helicobacter pylori Dampens HLA-II Expression on Macrophages via the Up-Regulation of miRNAs Targeting CIITA Frontiers in Immunology Helicobacter pylori miRNA macrophages antigen presentation gastric cancer |
| title | Helicobacter pylori Dampens HLA-II Expression on Macrophages via the Up-Regulation of miRNAs Targeting CIITA |
| title_full | Helicobacter pylori Dampens HLA-II Expression on Macrophages via the Up-Regulation of miRNAs Targeting CIITA |
| title_fullStr | Helicobacter pylori Dampens HLA-II Expression on Macrophages via the Up-Regulation of miRNAs Targeting CIITA |
| title_full_unstemmed | Helicobacter pylori Dampens HLA-II Expression on Macrophages via the Up-Regulation of miRNAs Targeting CIITA |
| title_short | Helicobacter pylori Dampens HLA-II Expression on Macrophages via the Up-Regulation of miRNAs Targeting CIITA |
| title_sort | helicobacter pylori dampens hla ii expression on macrophages via the up regulation of mirnas targeting ciita |
| topic | Helicobacter pylori miRNA macrophages antigen presentation gastric cancer |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02923/full |
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