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Myeloid Cell CK2 Regulates Inflammation and Resistance to Bacterial Infection

Kinase activity plays an essential role in the regulation of immune cell defenses against pathogens. The protein kinase CK2 (formerly casein kinase II) is an evolutionarily conserved kinase with hundreds of identified substrates. CK2 is ubiquitously expressed in somatic and immune cells, but the rol...

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Autores principales: Larson, Sandy R., Bortell, Nikki, Illies, Alysha, Crisler, William J., Matsuda, Jennifer L., Lenz, Laurel L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752951/
https://www.ncbi.nlm.nih.gov/pubmed/33363536
http://dx.doi.org/10.3389/fimmu.2020.590266
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author Larson, Sandy R.
Bortell, Nikki
Illies, Alysha
Crisler, William J.
Matsuda, Jennifer L.
Lenz, Laurel L.
author_facet Larson, Sandy R.
Bortell, Nikki
Illies, Alysha
Crisler, William J.
Matsuda, Jennifer L.
Lenz, Laurel L.
author_sort Larson, Sandy R.
collection PubMed
description Kinase activity plays an essential role in the regulation of immune cell defenses against pathogens. The protein kinase CK2 (formerly casein kinase II) is an evolutionarily conserved kinase with hundreds of identified substrates. CK2 is ubiquitously expressed in somatic and immune cells, but the roles of CK2 in regulation of immune cell function remain largely elusive. This reflects the essential role of CK2 in organismal development and limited prior work with conditional CK2 mutant murine models. Here, we generated mice with a conditional (floxed) allele of Csnk2a, which encodes the catalytic CK2α subunit of CK2. When crossed to Lyz2-cre mice, excision of Csnk2a sequence impaired CK2α expression in myeloid cells but failed to detectably alter myeloid cell development. By contrast, deficiency for CK2α increased inflammatory myeloid cell recruitment, activation, and resistance following systemic Listeria monocytogenes (Lm) infection. Results from mixed chimera experiments indicated that CK2α deficiency in only a subset of myeloid cells was not sufficient to reduce bacterial burdens. Nor did cell-intrinsic deficiency for CK2α suffice to alter accumulation or activation of monocytes and neutrophils in infected tissues. These data suggest that CK2α expression by Lyz2-expressing cells promotes inflammatory and anti-bacterial responses through effects in trans. Our results highlight previously undescribed suppressive effects of CK2 activity on inflammatory myeloid cell responses and illustrate that cell-extrinsic effects of CK2 can shape inflammatory and protective innate immune responses.
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spelling pubmed-77529512020-12-23 Myeloid Cell CK2 Regulates Inflammation and Resistance to Bacterial Infection Larson, Sandy R. Bortell, Nikki Illies, Alysha Crisler, William J. Matsuda, Jennifer L. Lenz, Laurel L. Front Immunol Immunology Kinase activity plays an essential role in the regulation of immune cell defenses against pathogens. The protein kinase CK2 (formerly casein kinase II) is an evolutionarily conserved kinase with hundreds of identified substrates. CK2 is ubiquitously expressed in somatic and immune cells, but the roles of CK2 in regulation of immune cell function remain largely elusive. This reflects the essential role of CK2 in organismal development and limited prior work with conditional CK2 mutant murine models. Here, we generated mice with a conditional (floxed) allele of Csnk2a, which encodes the catalytic CK2α subunit of CK2. When crossed to Lyz2-cre mice, excision of Csnk2a sequence impaired CK2α expression in myeloid cells but failed to detectably alter myeloid cell development. By contrast, deficiency for CK2α increased inflammatory myeloid cell recruitment, activation, and resistance following systemic Listeria monocytogenes (Lm) infection. Results from mixed chimera experiments indicated that CK2α deficiency in only a subset of myeloid cells was not sufficient to reduce bacterial burdens. Nor did cell-intrinsic deficiency for CK2α suffice to alter accumulation or activation of monocytes and neutrophils in infected tissues. These data suggest that CK2α expression by Lyz2-expressing cells promotes inflammatory and anti-bacterial responses through effects in trans. Our results highlight previously undescribed suppressive effects of CK2 activity on inflammatory myeloid cell responses and illustrate that cell-extrinsic effects of CK2 can shape inflammatory and protective innate immune responses. Frontiers Media S.A. 2020-12-08 /pmc/articles/PMC7752951/ /pubmed/33363536 http://dx.doi.org/10.3389/fimmu.2020.590266 Text en Copyright © 2020 Larson, Bortell, Illies, Crisler, Matsuda and Lenz http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Larson, Sandy R.
Bortell, Nikki
Illies, Alysha
Crisler, William J.
Matsuda, Jennifer L.
Lenz, Laurel L.
Myeloid Cell CK2 Regulates Inflammation and Resistance to Bacterial Infection
title Myeloid Cell CK2 Regulates Inflammation and Resistance to Bacterial Infection
title_full Myeloid Cell CK2 Regulates Inflammation and Resistance to Bacterial Infection
title_fullStr Myeloid Cell CK2 Regulates Inflammation and Resistance to Bacterial Infection
title_full_unstemmed Myeloid Cell CK2 Regulates Inflammation and Resistance to Bacterial Infection
title_short Myeloid Cell CK2 Regulates Inflammation and Resistance to Bacterial Infection
title_sort myeloid cell ck2 regulates inflammation and resistance to bacterial infection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752951/
https://www.ncbi.nlm.nih.gov/pubmed/33363536
http://dx.doi.org/10.3389/fimmu.2020.590266
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