TY - JOUR
T1 - Myeloid miR-155 plays a limited role in antibacterial defense during Klebsiella-derived pneumosepsis and is dispensable for lipopolysaccharide- or Klebsiella-induced inflammation in mice
AU - Qin, Wanhai
AU - Saris, Anno
AU - van 't Veer, Cornelis
AU - Roelofs, Joris J. T. H.
AU - Scicluna, Brendon P.
AU - de Vos, Alex F.
AU - van der Poll, Tom
N1 - Funding Information: W.Q. was funded by the Chinese Scholarship Council (CSC #20160617115). Funding Information: The authors thank Marieke S. ten Brink for helping with the animal experiments and Regina de Beer and Jacky the Leeuw for technical assistance. W.Q. was funded by the Chinese Scholarship Council (CSC #20160617115). Publisher Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.
PY - 2023/1/17
Y1 - 2023/1/17
N2 - MicroRNA-155 (miR-155) plays a crucial role in regulating host inflammatory responses during bacterial infection. Previous studies have shown that constitutive miR-155 deficiency alleviates inflammation while having varying effects in different bacterial infection models. However, whether miR-155 in myeloid cells is involved in the regulation of inflammatory and antibacterial responses is largely elusive. Mice with myeloid cell specific miR-155 deficiency were generated to study the in vitro response of bone marrow-derived macrophages (BMDMs), alveolar macrophages (AMs) and peritoneal macrophages (PMs) to lipopolysaccharide (LPS), and the in vivo response after intranasal or intraperitoneal challenge with LPS or infection with Klebsiella (K.) pneumoniae via the airways. MiR-155-deficient macrophages released less inflammatory cytokines than control macrophages upon stimulation with LPS in vitro. However, the in vivo inflammatory cytokine response to LPS or K. pneumoniae was not affected by myeloid miR-155 deficiency. Moreover, bacterial outgrowth in the lungs was not altered in myeloid miR-155-deficient mice, but Klebsiella loads in the liver of these mice were significantly higher than in control mice. These data argue against a major role for myeloid miR-155 in host inflammatory responses during LPS-induced inflammation and K. pneumoniae-induced pneumosepsis but suggest that myeloid miR-155 contributes to host defense against Klebsiella infection in the liver.
AB - MicroRNA-155 (miR-155) plays a crucial role in regulating host inflammatory responses during bacterial infection. Previous studies have shown that constitutive miR-155 deficiency alleviates inflammation while having varying effects in different bacterial infection models. However, whether miR-155 in myeloid cells is involved in the regulation of inflammatory and antibacterial responses is largely elusive. Mice with myeloid cell specific miR-155 deficiency were generated to study the in vitro response of bone marrow-derived macrophages (BMDMs), alveolar macrophages (AMs) and peritoneal macrophages (PMs) to lipopolysaccharide (LPS), and the in vivo response after intranasal or intraperitoneal challenge with LPS or infection with Klebsiella (K.) pneumoniae via the airways. MiR-155-deficient macrophages released less inflammatory cytokines than control macrophages upon stimulation with LPS in vitro. However, the in vivo inflammatory cytokine response to LPS or K. pneumoniae was not affected by myeloid miR-155 deficiency. Moreover, bacterial outgrowth in the lungs was not altered in myeloid miR-155-deficient mice, but Klebsiella loads in the liver of these mice were significantly higher than in control mice. These data argue against a major role for myeloid miR-155 in host inflammatory responses during LPS-induced inflammation and K. pneumoniae-induced pneumosepsis but suggest that myeloid miR-155 contributes to host defense against Klebsiella infection in the liver.
KW - anti-bacterial defense
KW - inflammatory responses
KW - lung inflammation
KW - miR-155
KW - myeloid cells
KW - pneumosepsis
UR - http://www.scopus.com/inward/record.url?scp=85176507944&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/femspd/ftad031
DO - https://doi.org/10.1093/femspd/ftad031
M3 - Article
C2 - 37858304
SN - 2049-632X
VL - 81
JO - Pathogens and Disease
JF - Pathogens and Disease
M1 - ftad031
ER -