Activation and cytokine profile of monocyte derived dendritic cells in leprosy: in vitro stimulation by sonicated Mycobacterium leprae induces decreased level of IL-12p70 in lepromatous leprosy

Abstract

Dendritic cells (DCs) play a pivotal role in the connection of innate and adaptive immunity of hosts to mycobacterial infection. Studies on the interaction of monocyte-derived DCs (MO-DCs) using Mycobacterium leprae in leprosy patients are rare. The present study demonstrated that the differentiation of MOs to DCs was similar in all forms of leprosy compared to normal healthy individuals. In vitro stimulation of immature MO-DCs with sonicated M. leprae induced variable degrees of DC maturation as determined by the increased expression of HLA-DR, CD40, CD80 and CD86, but not CD83, in all studied groups. The production of different cytokines by the MO-DCs appeared similar in all of the studied groups under similar conditions. However, the production of interleukin (IL)-12p70 by MO-DCs from lepromatous (LL) leprosy patients after in vitro stimulation with M. leprae was lower than tuberculoid leprosy patients and healthy individuals, even after CD40 ligation with CD40 ligand-transfected cells. The present cumulative findings suggest that the MO-DCs of LL patients are generally a weak producer of IL-12p70 despite the moderate activating properties ofM. leprae. These results may explain the poor M. leprae-specific cell-mediated immunity in the LL type of leprosy.

Host Lipid Mediators in Leprosy: The Hypothesized Contributions to Pathogenesis

“…Besides a direct effect on T cells, PGD 2 modulates the T-cell response through dendritic cells and their production of IL-12 ( 19 , 59 ). Braga et al has revealed that monocyte-derived dendritic cells from LL patients produced less IL-12 ( 25 ), and although a direct association has not been made, the decreased IL-12 levels in LL patients could be driven by increased PGD 2 production and secretion by foamy macrophages/Schwann cells (Figure 5 ).…”

Association of CD209 (DC-SIGN) rs735240 SNV with paucibacillary leprosy in the Brazilian population and its functional effects

“…Functional evaluation -To evaluate the functional effects of the rs735240 SNV on the immune response against M. leprae, we analysed the expression levels of DC-SIGN, cytokines, and other accessory molecules using data from two previous and independent studies from our group. (47,48) First, we examined the mRNA expression levels in 28 leprosy patients [Supplementary data (Table I)] according to the presence or absence of allele A of rs735240 using the dataset GSE74481. (47) In brief, biopsies from leprosy skin lesions were collected and stored in RNAlater solution (Ambion).…”

“…We also explored the expression of DC-SIGN, cytokines, and other surface markers by monocyte-derived DCs from leprosy patients primed with M. leprae antigen (48) [Supplementary data (Table II)], taking into account the genotype of rs735240. In this study, monocytes from leprosy patients were purified from peripheral blood and treated with GM-CSF and IL-4 to differentiate into DCs that were stimulated by M. leprae sonicated antigen or standard maturation cocktail (IL-1β, IL-6, tumor necrosis factor, and prostaglandin E2), or remained unstimulated.…”

In search of biomarkers for leprosy by unraveling the host immune response to Mycobacterium leprae

“…It is well described that via the production of IL‐12 by DCs, T cells start to produce IFN‐γ indicative of an effective Th1 response. Although in vitro differentiation of monocytes to DCs was similar for lepromatous and tuberculoid patients, the production of IL‐12 in response to M leprae was weak in lepromatous patients, in conjunction with the lack of cellular‐mediated immunity at this site of the leprosy spectrum 119 …”

“…Although in vitro differentiation of monocytes to DCs was similar for lepromatous and tuberculoid patients, the production of IL-12 in response to M leprae was weak in lepromatous patients, in conjunction with the lack of cellular-mediated immunity at this site of the leprosy spectrum. 119 Recently, it has been shown that monocytes can also differentiate to DCs in an IL-32-dependent manner; these DCs are more efficient in antigen presentation to MHC class I-restricted CD8 T-cells compared to the GM-CSF-induced DCs. 120 The NOD2 receptor on monocytes recognizes the muramyl dipeptides (MDPs) from M leprae, inducing the production of IL-32 and the subsequent differentiation to DCs.…”