| First Author | Parihar SP | Year | 2018 |
| Journal | Mucosal Immunol | Volume | 11 |
| Issue | 2 | Pages | 496-511 |
| PubMed ID | 28832027 | Mgi Jnum | J:330321 |
| Mgi Id | MGI:6823036 | Doi | 10.1038/mi.2017.68 |
| Citation | Parihar SP, et al. (2018) Protein kinase C-delta (PKCdelta), a marker of inflammation and tuberculosis disease progression in humans, is important for optimal macrophage killing effector functions and survival in mice. Mucosal Immunol 11(2):496-511 |
| abstractText | We previously demonstrated that protein kinase C-delta (PKCdelta) is critical for immunity against Listeria monocytogenes, Leishmania major, and Candida albicans infection in mice. However, the functional relevance of PKCdelta during Mycobacterium tuberculosis (Mtb) infection is unknown. PKCdelta was significantly upregulated in whole blood of patients with active tuberculosis (TB) disease. Lung proteomics further revealed that PKCdelta was highly abundant in the necrotic and cavitory regions of TB granulomas in multidrug-resistant human participants. In murine Mtb infection studies, PKCdelta(-/-) mice were highly susceptible to tuberculosis with increased mortality, weight loss, exacerbated lung pathology, uncontrolled proinflammatory cytokine responses, and increased mycobacterial burdens. Moreover, these mice displayed a significant reduction in alveolar macrophages, dendritic cells, and decreased accumulation of lipid bodies (lungs and macrophages) and serum fatty acids. Furthermore, a peptide inhibitor of PKCdelta in wild-type mice mirrored lung inflammation identical to infected PKCdelta(-/-) mice. Mechanistically, increased bacterial growth in macrophages from PKCdelta(-/-) mice was associated with a decline in killing effector functions independent of phagosome maturation and autophagy. Taken together, these data suggest that PKCdelta is a marker of inflammation during active TB disease in humans and required for optimal macrophage killing effector functions and host protection during Mtb infection in mice. |
