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

Tom van der Poll,Cornelis van’t Veer,Wanhai Qin,Brendon P. Scicluna,Xanthe Brands,Alex F. de Vos

doi:10.3390/cells11050787

Tom van der Poll, Cornelis van’t Veer + Show 4 more

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https://doi.org/10.3390/cells11050787

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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.

Highlights

Bacterial loads and neutrophil numbers in bronchoalveolar lavage fluid (BALF) were similar in both mouse strains at 6 and 24 h after infection (Figure 1A,B)
DNA methyltransferase 3b (Dnmt3b) in host defense to P. aeruginosa infection [8–10], the data presented here strongly argue against the role of myeloid Dnmt3b in Pseudomonas pneumonia
It was demonstrated that knock-down of Dnmt3b in macrophages resulted in decreased expres

Summary

Introduction

DNA methyltransferase 3b (Dnmt3b) has been suggested to play a role in the host immune response during bacterial 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/fl Mrp8Cre ) or myeloid cell-specific (Dnmt3bfl/fl LysMCre ) Dnmt3b-deficient mice and littermate control mice were infected with P. aeruginosa PAK via the airways. 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. Dnmt3b deficiency in neutrophils or myeloid cells does not affect acute immune responses in the airways during Pseudomonas pneumonia

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