| First Author | Guler R | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 3 | Pages | 706-15 |
| PubMed ID | 21287553 | Mgi Jnum | J:175423 |
| Mgi Id | MGI:5285507 | Doi | 10.1002/eji.201040985 |
| Citation | Guler R, et al. (2011) PKCdelta regulates IL-12p40/p70 production by macrophages and dendritic cells, driving a type 1 healer phenotype in cutaneous leishmaniasis. Eur J Immunol 41(3):706-15 |
| abstractText | The protein kinase C (PKC) family is involved in the regulation of many intracellular signalling pathways. Here, we report that the PKCdelta isoform regulates IL-12p40/p70 production in macrophages and DC and that PKCdelta deficiency in mice transforms the 129/Sv healer to a non-healer strain during cutaneous leishmaniasis. Leishmania major-infected PKCdelta(-/-) 129/Sv mice developed a rapid increase in footpad swelling and parasite burden with disease progression, leading to necrosis and ulceration similar to non-healer BALB/c mice. Moreover, PKCdelta(-/-) mice failed to develop delayed-type hypersensitivity responses against Leishmania antigen. PKCdelta(-/-) macrophages were fully functional with normal MHC class II surface expression and GM-CSF production, recruitment to the draining lymph node and killing effector functions by NO production. In contrast, macrophages and DC produced significantly reduced IL-12p40 and IL-12p70 compared to the WT cells. Decreased IL-12 production resulted in diminished Th1 differentiation, as determined by a striking reduction in IFN-gamma by antigen-specific stimulated CD4(+) T cells isolated from popliteal lymph nodes of L. major-infected PKCdelta(-/-) mice, explaining the 'non-healer' phenotype. We conclude from these data that PKCdelta is a regulator of IL-12p40/p70 production by DC and macrophages, driving the healer phenotype during cutaneous leishmaniasis. |
