ABSTRACT
Peripheral blood mononuclear cells in lepromatous leprosy (LL) patients produce low levels of interferon-gamma (IFN-gamma) and interleukin-12 (IL-12), and these cells exhibit partial or complete deficiency in the IL-12 receptor. The behavior of the IFN-gamma receptor (IFN-gamma R) has not been described in cells from people with leprosy. We found higher levels of mRNA for IFN-gamma R1 and IFN-gamma R2 in adherent cells stimulated with IFN-gamma and Mycobacterium leprae membrane proteins from LL patients compared with healthy subjects. Flow cytometry showed no significant difference in IFN-gamma R1 expression between LL patients and healthy subjects. Immunoblotting detected only the mature glycosylated form of the 61-67 kDa IFN-gamma R2 protein in healthy subjects. In contrast, cells from LL patients showed three different expression patterns: (1) the immature deglycosylated form of the 34.8 kDa IFN-gamma R2 protein, (2) the mature glycosylated 61-67 kDa form, and (3) both forms. Our data indicate the existence of abnormalities in the intracellular processing and protein expression of the IFN-gamma R in response to specific stimuli such as IFN-gamma and M. leprae membrane proteins in adherent cells of LL patients.
Subject(s)
Leprosy, Lepromatous/metabolism , Leprosy, Lepromatous/pathology , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/pathology , Receptors, Interferon/genetics , Receptors, Interferon/metabolism , Adult , Cell Adhesion , Female , HeLa Cells , Humans , Male , Middle Aged , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Interferon/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Interferon gamma ReceptorABSTRACT
Patterns of production of specific cytokines are accepted as standards for T-lymphocyte subsets in diseases caused by intracellular parasites. These lymphocyte subsets (Th1 and Th2) have been associated with the different poles of the leprosy spectrum. Lepromatous leprosy (LL) onset correlates with cytokines produced by Th2 cells on the grounds of the patient's poor cellular immune response, i.e., interleukin 2 (IL-2) and gamma interferon (IFN-gamma) deficiency. On the other hand, tuberculoid leprosy (TL) has been associated with a Th1 response. Moreover, pro-inflammatory cytokines like IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) play a major role in chronic inflammatory pathologies being IL-1ra and TNF-alpha soluble receptors, natural counterbalancing inhibitors. In light of this background, we decided to measure serum levels of IL-1 beta, IL-1ra, TNF-alpha and IL-6 in LL and TL patients, and we also studied the production in vitro of Th1 (IFN-gamma, IL-2), Th2 (IL-4, IL-10) and TNF-alpha cytokines. Our data showed that IL-1ra is highly elevated in sera from LL patients; there were no differences in Th2 cytokine levels and there were diminished levels in Th1 cytokines.
