Serum Levels of Migration Inhibitory Factor (MIF) and In Situ Expression of MIF and Its Receptor CD74 in Lepromatous Leprosy Patients: A Preliminary Report.

Leprosy is a chronic disease caused by Mycobacterium leprae that affects the skin and peripheral nerves. It may present as one of two distinct poles: the self-limiting tuberculoid leprosy and the highly infectious lepromatous leprosy (LL) characterized by M. leprae-specific absence of cellular immune response. The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) enhance the bactericide activities of macrophages after interaction with its receptor, CD74. Importantly, MIF also possesses chemoattractant properties, and it is a key factor in situ for the activation of macrophages and in blood to promote leukocytes migration. MIF-mediated activation of macrophages is a key process for the elimination of pathogens such as Mycobacterium tuberculosis; however, its participation for the clearance of M. leprae is unclear. The aim of this study was to evaluate the serum levels of MIF as well as MIF and CD74 expression in skin lesions of LL and compare it with healthy skin (HSk) taken from subjects attending to dermatological consult. Samples of serum and skin biopsies were taken from 39 LL patients and compared with 36 serum samples of healthy subjects (HS) and 10 biopsies of HSk. Serum samples were analyzed by ELISA and skin biopsies by immunohistochemistry (IHC). IHC smears were observed in 12 100× microscopic fields, in which percentage of stained cells and staining intensity were evaluated. Both variables were used to calculate a semi-quantitative expression score that ranged from 0 to 3+. We found no differences in MIF levels between LL patients and HS in sera. In addition, MIF was observed in over 75% of cells with high intensity in the skin of patients and HSk. Although we found no differences in MIF expression between the groups, a CD74 score statistically higher was found in LL skin than HSk (p < 0.001); this was the result of a higher percentage of cells positive for CD74 (p < 0.001). As a conclusion, we found that CD74-positive cells are intensely recruited to the skin with LL lesions. In this manner, MIF signaling may be enhanced in the skin of LL patients due to increased expression of its receptor, but further studies are required.

Abnormalities in intracellular processing and expression of interferon-gamma receptor in adherent cells from lepromatous leprosy patients.

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.