Inhibition of Lipopolysaccharide-Induced Macrophage IL-12 Production by Leishmania mexicana Amastigotes: The Role of Cysteine Peptidases and the NF-κB Signaling Pathway

• DOI: 10.4049/jimmunol.173.5.3297
• Publication Date: 2014-04-21T00:03:38Z
• Authors: Pamela Cameron; Adrienne McGachy; Mary Anderson; Andrew Paul; Graham H Coombs; Jeremy C Mottram; James Alexander; Robin Plevin
• Keywords: Amastigote; Leishmania mexicana; IκBα

Abstract Infection with lesion-derived Leishmania mexicana amastigotes inhibited LPS-induced IL-12 production by mouse bone marrow-derived macrophages. This effect was associated expression of cysteine peptidase B (CPB) because CPB deletion mutants had limited ability to inhibit production, whereas preincubation cells a inhibitor, cathepsin inhibitor IV, able suppress the wild-type amastigotes. resulted in time-dependent proteolytic degradation IκBα and IκBβ related protein NF-κB. did not occur or promastigotes, which do express detectable CPB. NF-κB DNA binding also amastigote infection, although nuclear translocation cleaved fragments p65 still observed. Cysteine inhibitors prevented IκBα, IκBβ, induced amastigotes, recombinant CPB2.8, an amastigote-specific isoenzyme CPB, shown degrade GST-IκBα vitro. LPS-mediated affected these inhibitors, confirming that site receptor-driven, proteosomal-mediated cleavage. marrow macrophages cleavage JNK ERK, but p38 MAPK, proteins, result enhanced kinase activation. Collectively, our results suggest peptidases L. are central parasite modulate signaling via consequently production.