Effect of LACK and KMP11 on IFN-γ Production by Peripheral Blood Mononuclear Cells from Cutaneous and Mucosal Leishmaniasis Patients

Abstract

The immune modulatory properties of recombinant antigens Kinetoplasmid membrane protein-11 (KMP11) and Leishmania homologue of receptors for activated C kinase (LACK) in cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) patients were evaluated. The mean levels of interferon-γ (IFN-γ) in soluble leishmania antigen (SLA) stimulated peripheral blood mononuclear cells (PBMC) of ML and CL patients were 5625 ± 2333 pg/ml and 4422 ± 3665 pg/ml, respectively. IFN-γ was not detected in cultures stimulated with KMP11 or LACK. Interleukin-10 (IL-10) concentration in SLA, KMP11 and LACK-stimulated PBMC of ML patients was 13 ± 12 pg/ml, 285 ± 388 pg/ml and 802 ± 483 pg/ml, respectively. Addition of KMP11 or LACK to SLA-stimulated PBMC of CL and ML patients enhanced IL-10 production (P < 0.05). Addition of KMP11 decreased IFN-γ levels by 52% in CL patients and by 19% in ML patients. Addition of LACK to SLA-stimulated cultures decreased IFN-γ levels by 58% in CL patients and by 30% in ML patients. Neutralization of IL-10 abrogated the downregulatory effect of LACK and KMP11. The modulatory properties of LACK and KMP11 are due to induction of IL-10 production and may be helpful for attenuating chronic inflammatory diseases. However, in some clinical conditions, as demonstrated for ML, these molecules are not able to suppress the IFN-γ response, even inducing IL-10 production.