Myeloid Cell CK2 Regulates Inflammation and Resistance to Bacterial Infection

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• Kinase activity is crucial for immune cell defense against pathogens.
• Protein kinase CK2 (CK2) is vital for cellular functions but its role in immune regulation is unclear.
• CK2 is essential for development, limiting studies on its immune function using mutant models.

Purpose of the Study:

• To investigate the role of CK2α in myeloid cell function and immune responses.
• To determine if CK2α deficiency impacts immune cell development and inflammatory responses.
• To elucidate the cell-intrinsic and cell-extrinsic roles of CK2α in innate immunity.

Main Methods:

• Generated conditional CK2α-deficient mice (floxed Csnk2a allele) crossed with Lyz2-cre mice.
• Analyzed myeloid cell development and inflammatory responses following Listeria monocytogenes infection.
• Utilized mixed chimera experiments to assess cell-intrinsic versus cell-extrinsic effects.

Main Results:

• CK2α deficiency in myeloid cells did not alter their development but increased inflammatory cell recruitment, activation, and resistance to Listeria monocytogenes.
• CK2α deficiency in a subset of myeloid cells or cell-intrinsically did not reduce bacterial burden.
• CK2α expression by Lyz2-expressing cells promotes inflammatory and antibacterial responses via trans effects.

Conclusions:

• CK2 activity suppresses inflammatory myeloid cell responses.
• Cell-extrinsic effects of CK2 are critical in shaping innate immune responses.
• CK2α plays a previously unrecognized suppressive role in innate immunity.