SCD163 levels as a biomarker of disease severity in leprosy and visceral leishmaniasis.

Ricardo Luís Louzada Silva,Jaqueline França-Costa,Priscila L S Almeida,Marcio B Santos,Michael W Lipscomb,Thayse S Barros,Amélia Ribeiro Jesus,Patrícia R M Souza,Roque Pacheco Almeida,Malcolm S Duthie,Djalma S Lima-Junior,Lucas Magalhães,Nívea F Luz,Steven G Reed,Valeria M Borges,Rodrigo A Cazzaniga,Edgar M Carvalho

doi:10.1371/journal.pntd.0005486

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.

Highlights

CD163 is a member of the scavenger receptor cysteine-rich family [1]
Our results reveal soluble form of CD163 (sCD163) as a potential biomarker of severity of diseases caused by intracellular pathogens M. leprae and Leishmania spp. and have a modulatory
Receiver Operating Characteristic (ROC) curves were constructed and area under the curve (AUC) analysis highlighted the utility of sCD163 levels for distinguishing between lepromatous leprosy (LL) and either TT (AUC = 0.8571, 95% confidence interval (CI) [0.69–1.02], p = 0.0034) or contacts (AUC = 0.8439, 95% CI [0.72–1.02], p = 0.0008) (Fig 1B and 1C)

Summary

Introduction

CD163 is a member of the scavenger receptor cysteine-rich family [1]. CD163 binds to hemoglobin (Hb) and haptoglobin (Hp) complex [2] and helps to coordinate the receptor-mediated endocytosis by phagocytes [3] to be processed by hemeoxygenase-1 (HO-1) [4,5]. CD163 can be shed from the macrophage surface in response to inflammatory stimuli [3], and can be found as a soluble form (i.e. sCD163) [7,11]. Macrophages expressing CD163 have been described in lepromatous leprosy (LL), the most severe presentation of the infectious disease caused by Mycobacterium leprae, with CD163 facilitating bacterial survival by providing a source of iron for mycobacterial survival as well as triggering IL-10 production [7]. CD163, 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. We hypothesized that sCD163 correlates with severity of diseases caused by intracellular pathogens.

Methods

Results

Discussion

Conclusion