The Role Of Protein Kinase C-? In Innate Immunity To Infection

Protein kinase C(PKC)is an important famlily of serine/threonine kinases.PKCs participate in a variety of important physiological and biochemical processes.Our study focused on the role of PKC-? in the innate immunity.In particular,we investigated the role of PKC-? in anti-TB and anti-fungal innate immunity.It is widely accepted that macrophages and neutrophils play an important role in innateimmunity.Tuberculosis caused by Mycobacterium tuberculosis infection and invasive fungal infection caused by Candida albicans infection are seriously jeopardizing human health and quality of life.To investigate the role of PKC-? in anti-TB innate immunity,we treated macrophages with TDB in vitro and found that:(1)TDB-induced TNFa production in PKC-?-/-BMDM was significantly reduced compared with WT.(2)TNFa mRNA transcription in PKC-?-/-BMDM was significantly reduced compared with WT.(3)TDB induced a marked IKBa degradation in PKC-?-/-BMDM compared with WT.(4)TDB induced the expression of mincle protein in WT but not PKC-?-/-BMDM.(5)Mincle mRNA transcription in PKC-?-/-BMDM was significantly reduced compared with WT.To investigate the role of PKC-? in anti-fungal innate immunity,we infected WT and PKC-?-/-mice with C.albicans in vivo and found that:(1)Mortality increased significantly in PKC-8-/-mice compared to WT mice.(2)Kidney abscess and bacterial burden increased significantly in PKC-?-/-mice compared to WT mice.(3)There are significantly more fungal growth and inflammatory cell infiltration in the renal tissue of PKC-?-/-mice.In addition,we treated neutrophils with zymosan in vitro and found that:(1)The ability of PKC-?-/-neutrophils to kill Candida albicans was reduced compared to WT.(2)Phagocytosis of Candida albicans by neutrophils did not depend on PKC-8.(3)Zymosan induced a marked decrease in ROS production by PKC-?-/-neutrophils compared with WT.In summary,the results showed that PKC-8 plays an important role in innate immunity against Mycobacterium tuberculosis and Candida albicans infection.