Constitutively expressed MHC class Ib molecules regulate macrophage M2b polarization and sepsis severity in irradiated mice

Macrophages can change their physiology in response to microenvironmental signals. This differentiation into classically activated M1 or alternatively activated M2 macrophages is known as polarization. In this study, we isolated bone marrow‐derived macrophages from β2m‐deficient (deficient in both MHC class Ia and Ib) and KbDb‐deficient (deficient only in MHC class Ia) mice and found that β2m‐deficient macrophages showed a significantly lower M2b polarization efficiency. In addition, the absence of constitutive MHC class Ib expression decreased the stability of the Notch‐1 intracellular domain. Finally, we found that β2m‐deficient mice exposed to irradiation showed reduced bacterial translocation and sepsis severity. Overall, our study demonstrates that MHC class Ib molecules are essential for M2b macrophage polarization and suggests that MHC class Ib molecules play an important role during infection‐induced innate immunity. Constitutively expressed MHC class Ib regulate macrophage polarization into M2b profiles, and play an important role in bacterial translocation and subsequent sepsis in mice exposed to irradiation.