sCD163 levels as a biomarker of disease severity in leprosy and visceral leishmaniasis

Abstract

BackgroundCD163, receptor for the haptoglobin–hemoglobin complex, is expressed on monocytes/macrophages and neutrophils. A soluble form of CD163 (sCD163) has been associated with the M2 macrophage phenotype, and M2 macrophages have been shown to down-modulate inflammatory responses. In particular, previous studies have shown that M2 is closely associated with the most severe clinical presentation of leprosy (i.e. lepromatous leprosy (LL)), as well as tuberculosis. We hypothesized that sCD163 correlates with severity of diseases caused by intracellular pathogens.Methodology/Principal findingsTo assess this hypothesis, sCD163 levels were measured in the serum of leprosy and visceral leishmaniasis (VL) patients stratified by severity of the clinical presentation. sCD163 levels were significantly higher in patients with these diseases than those observed in healthy control individuals. Further analyses on infection and disease status of leprosy and VL patients revealed a clear association of sCD163 levels with clinical parameters of disease severity. In vitro culture assays revealed that Leishmania infection induced CD163 expression on the surface of both monocyte/macrophages and neutrophils, suggesting these cells as possible sources of sCD163. FACS analyses shows that the cells expressing CD163 produces both TNF-α and IL-4.Conclusions/SignificanceTaken together, our results reveal sCD163 as a potential biomarker of severity of diseases caused by intracellular pathogens M. leprae and Leishmania spp. and have a modulatory role, with a mix of an inflammatory property induced by TNF-α release, but that potentially induces an anti-inflammatory T cell response, related to IL-4 release.

An IL‐10 dominant polarization of monocytes is a feature of Indian Visceral Leishmaniasis

“…32 Although the frequency of CD163 + within the CD14 + population remained unaltered, Figure 2C, the soluble form, sCD163 was substantially increased Figure 2D, and negatively correlated with plasma IL-10, r = −.70, Figure 2E. Although sCD163 is considered as a marker of inflammation, 33 its increase has been associated with disease severity in VL 34 and may be attributed to the increased uptake of haem via CD163 leading to its subsequent shedding. Another putative contributor for sCD163 could be the raised levels of antileishmanial antibodies, 21 and was endorsed by its positive correlation with OD 405 of antileishmanial IgG, r = .46.…”

Salivary Gland Extract Modulates the Infection of Two Leishmania enriettii Strains by Interfering With Macrophage Differentiation in the Model of Cavia porcellus

“…This receptor has been identified as an indicator of anti-inflammatory macrophages (M2 macrophages) ( Kristiansen et al, 2001 ). Silva et al (2017) demonstrated that in VL, the levels of soluble CD163 (sCD163) may serve as a biomarker for the severity of the disease in various inflammatory disorders. Its level was increased in VL patients and was directly correlated with clinical parameters of disease severity.…”

Macrophage Polarization in Leishmaniasis: Broadening Horizons

“…In the same direction, Silva et al ( 102 ) demonstrated that the CD163s molecule was associated with the M2 macrophage phenotype, and it may be used as a biomarker of the clinical parameters of human VL severity. L. donovani also promotes the output of monocytes with a regulatory phenotype from the bone marrow that function as safe targets for the parasite ( 127 ).…”