DNA Methyltransferase 3b in Myeloid Cells Does Not Affect the Acute Immune Response in the Airways during Pseudomonas Pneumonia

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

DNA methyltransferase 3b (Dnmt3b) has been suggested to play a role in the host immune response during bacterial infection. Neutrophils and other myeloid cells are crucial for lung defense against Pseudomonas (P.) aeruginosa infection. This study aimed to investigate the role of Dnmt3b in neutrophils and myeloid cells during acute pneumonia caused by P. aeruginosa. Neutrophil-specific (Dnmt3bfl/flMrp8Cre) or myeloid cell-specific (Dnmt3bfl/flLysMCre) Dnmt3b-deficient mice and littermate control mice were infected with P. aeruginosa PAK via the airways. Bacteria burdens, neutrophil recruitment, and activation (CD11b expression, myeloperoxidase, and elastase levels), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) were measured in bronchoalveolar lavage fluid (BALF) at 6 and 24 h after infection. Our data showed that the bacterial loads and neutrophil recruitment and activation did not differ in BALF obtained from neutrophil-specific Dnmt3b-deficient and control mice, whilst BALF IL-6 and TNF levels were lower in the former group at 24 but not at 6 h after infection. None of the host response parameters measured differed between myeloid cell-specific Dnmt3b-deficient and control mice. In conclusion, dnmt3b deficiency in neutrophils or myeloid cells does not affect acute immune responses in the airways during Pseudomonas pneumonia.

Related collections

Most cited references 23

Record: found
Abstract: found
Article: not found

Function and information content of DNA methylation.

Dirk Schübeler (2015)

Cytosine methylation is a DNA modification generally associated with transcriptional silencing. Factors that regulate methylation have been linked to human disease, yet how they contribute to malignances remains largely unknown. Genomic maps of DNA methylation have revealed unexpected dynamics at gene regulatory regions, including active demethylation by TET proteins at binding sites for transcription factors. These observations indicate that the underlying DNA sequence largely accounts for local patterns of methylation. As a result, this mark is highly informative when studying gene regulation in normal and diseased cells, and it can potentially function as a biomarker. Although these findings challenge the view that methylation is generally instructive for gene silencing, several open questions remain, including how methylation is targeted and recognized and in what context it affects genome readout.

0 comments Cited 458 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Comparative analysis of the efficiency and specificity of myeloid-Cre deleting strains using ROSA-EYFP reporter mice.

Clare L. Abram, Gray L Roberge, YONGMEI HU … (2014)

Since the first example of conditional gene targeting in mice in 1994, the use of Cre recombinase and loxP flanked sequences has become an invaluable technique to generate tissue and temporal specific gene knockouts. The number of mouse strains expressing floxed-gene sequences, and tissue-specific or temporal-specific Cre-recombinase that have been reported in the literature has grown exponentially. However, increased use of this technology has highlighted several problems that can impact the interpretation of any phenotype observed in these mouse models. In particular, accurate knowledge of the specificity of Cre expression in each strain is critical in order to make conclusions about the role of specific cell types in the phenotypes observed. Cre-mediated deletion specificity and efficiency have been described in many different ways in the literature, making direct comparisons between these Cre strains impossible. Here we report crossing thirteen different myeloid-Cre mouse strains to ROSA-EYFP reporter mice and assaying YFP expression in a variety of naïve unstimulated hematopoietic cells, in parallel. By focusing on myeloid subsets, we directly compare the relative efficiency and specificity of myeloid deletion in these strains under steady-state conditions.

0 comments Cited 237 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Epigenetic regulation of macrophage polarization by DNA methyltransferase 3b.

Xiaosong Yang, Xianfeng Wang, Dongxu Liu … (2014)

Adipose tissue macrophages (ATMs) undergo a phenotypic switch from alternatively activated antiinflammatory M2 macrophages in lean individuals to classically activated proinflammatory M1 macrophages in obese subjects. However, the molecular mechanism underlying this process remains unclear. In this study we aim to determine whether DNA methyltransferase 3b (DNMT3b) regulates macrophage polarization and inflammation. We found that the expression of DNMT3b was significantly induced in macrophages exposed to the saturated fatty acid stearate, was higher in ATMs isolated from obese mice, but was significantly lower in alternatively activated M2 vs classically activated M1 ATMs, suggesting a role for DNMT3b in regulation of macrophage polarization and inflammation in obesity. DNMT3b knockdown promoted macrophage polarization to alternatively activated M2 phenotype and suppressed macrophage inflammation, whereas overexpressing DNMT3b did the opposite. Importantly, in a macrophage-adipocyte coculture system, we found that DNMT3b knockdown significantly improved adipocyte insulin signaling. The promoter of peroxisome proliferator activated receptor (PPAR)γ1, a key transcriptional factor that regulates macrophage polarization, is enriched with CpG sites. Chromatin immunoprecipitation assays showed that DNMT3b bound to the methylation region at PPARγ1 promoter, which was further enhanced by stearate. Moreover, pyrosequencing analysis revealed that stearate increased DNA methylation at PPARγ1, which was prevented by DNMT3b deficiency. Therefore, our data demonstrate that DNMT3b plays an important role in regulating macrophage polarization through epigenetic mechanisms. In obesity, elevated saturated fatty acids enhance DNMT3b expression, leading to DNA methylation at the PPARγ1 promoter, which may contribute to deregulated adipose tissue macrophage polarization, inflammation, and insulin resistance.

0 comments Cited 93 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Wanhai Qin: (View ORCID Profile)

Alex F. de Vos: (View ORCID Profile)

Journal

Journal ID (publisher-id): CELLC6

Title: Cells

Abbreviated Title: Cells

Publisher: MDPI AG

ISSN (Electronic): 2073-4409

Publication date Created: March 2022

Publication date (Electronic): February 24 2022

Volume: 11

Issue: 5

Page: 787

Article

DOI: 10.3390/cells11050787

SO-VID: 6aa99267-6afb-4649-85d1-5c5290352003

License:

https://creativecommons.org/licenses/by/4.0/

History

Data availability:

Comments

Comment on this article

scite_

Smart Citations

Citing PublicationsSupportingMentioningContrasting

View Citations

See how this article has been cited at scite.ai

scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.