Protein kinase C δ is essential for optimal macrophage-mediated phagosomal containment of Listeria monocytogenes

Activation of macrophages and subsequent killing effector functions against infectious pathogens are essential for the establishment of protective immunity. NF-lL6 is a transcription factor downstream of IFN-,gamma and TNF in the macrophage activation pathway required for bacterial killing. Comparison of microarray expression profiles of Listeria monocytogenes (LM)-infected macrophages from WT and NF-IL6-deficient mice enabled us to identify candidate genes downstream of NIF-IL6 involved in the unknown pathways of LM killing independent of reactive oxygen intermediates and reactive nitrogen intermediates. One differentially expressed gene, PKC delta, had higher mRNA levels in the LM-infected NF-IL6-deficient macrophages as compared with WT. To define the role of PKCS during listeriosis, we infected PKC delta-deficient mice with LM. PKC delta-deficient mice were highly susceptible to LM infection with increased bacterial burden and enhanced histopathology despite enhanced NF-IL6 mRNA expression. Subsequent studies in PKC delta-deficient macrophages demonstrated that, despite elevated levels of proinflammatory cytokines and NO production, increased escape of LM from the phagosome into the cytoplasm and uncontrolled bacterial growth occurred. Taken together these data identified PKC delta as a critical factor for confinement of LM within macrophage phagosomes.