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A Defective Oxidative Burst and Impaired Antigen Presentation are Hallmarks of Human Visceral Leishmaniasis.

Abstract：

PURPOSE:Survival of the Leishmania parasite within monocytes hinges on its ability to effectively nullify their microbicidal effector mechanisms. Accordingly, this study aimed to delineate this biological niche in patients with visceral leishmaniasis (VL). METHODS:In monocytes, the redox status, antigen presenting capacity, expression of Toll-like receptors (TLRs), co-stimulatory molecules (CD80/86) and generation of intracellular cytokines (IL-8, IL-1β, IL-10 and LAP-TGF-β1) was measured by flow cytometry, levels of circulating cytokines (IL-1β, IL-6, TNF-α, IL-8, IL-4, IL-13, IL-10 and GM-CSF) by ELISA and arginase activity by spectrophotometry. RESULTS:Within monocytes, generation of an oxidative burst was markedly attenuated as evident by decreased generation of nitric oxide and reactive oxygen species, concomitant with raised levels of thiols. This was accompanied by lowered frequency of TLR4(+) monocytes, but the arginase activity remained unaltered. Pathogen persistence was enhanced by the predominance of anti-inflammatory cytokines within monocytes, notably IL-10. Alongside, development of adaptive immunity was severely attenuated as manifested by a pronounced impairment of antigen presentation and co-stimulation evident by down regulation of CD54, HLA-DR and CD86. Treatment corrected the redox imbalance and reversed the impaired antigen presentation. CONCLUSIONS:In VL, monocyte functions were severely impaired facilitating parasite persistence; anti-leishmanial chemotherapy mediated parasite elimination through modulation of the macrophage microenvironment by restoring its redox status and antigen presenting capacity.

journal_name

J Clin Immunol

journal_title

Journal of clinical immunology

authors

Roy S,Mukhopadhyay D,Mukherjee S,Ghosh S,Kumar S,Sarkar K,Pal D,Bhowmik P,Mandal K,Modak D,Guha SK,Pramanik N,Goswami RP,Saha B,Chatterjee M

doi

10.1007/s10875-014-0115-3

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

56-67

issue

1

eissn

0271-9142

issn

1573-2592

pii

10.1007/s10875-014-0115-3

journal_volume

35

pub_type

杂志文章

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