Myeloid cells expressing CK2α modulates resistance to systemic Listeria monocytogenes infection

Autor: Sandy R Larson, Cris Crisler, Laurel L Lenz
Rok vydání: 2020
Předmět:
Zdroj: The Journal of Immunology. 204:227.13-227.13
ISSN: 1550-6606
0022-1767
Popis: Reversable phosphorylation is a key regulatory mechanism of nearly all cellular processes. Kinase activity driving phosphorylation has implications in cell growth, survival, development, differentiation, and importantly, immune responses to pathogens. The protein kinase CK2 (casein kinase II) is a ubiquitously expressed and highly conserved haloenzyme with over 500 direct target substrates identified. Because of this promiscuous activity, CK2 is extensively involved in immune cell function, described in both innate and adaptive immune cells. However, functionality of CK2 is not clearly delineated, largely due to the lack of murine models available for study. Engineered mice deficient in either the catalytic α or α′, or the regulatory β subunits are either non-viable or non-fertile. Therefore, we have generated a conditional murine knockout model of CK2α by cre-mediated excision in lysozyme M (LysM) expressing cells. Progeny are viable and fertile, with no deficiencies of immune cell populations. Using this model system, we have identified a role of CK2α in negatively regulating monocyte and neutrophil infiltration and endosome acidification during the bacterial Listeria monocytogenes (Lm) infection, correlating with uncontrolled bacterial replication. Further, decreased inflammatory myeloid cells in infected tissues is a cell-intrinsic effect of CK2α. Future work is aimed to understand the mechanisms by which CK2α negatively regulates the accumulation of immune cells in infected tissues. Additionally, we now have a tool for investigating in vivo effects of CK2α that we can use to extend beyond these initial studies to evaluate its role in other bacterial/viral infections, autoimmunity and even cancer.
Databáze: OpenAIRE
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