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

Roy, Susmita; Mukhopadhyay, Debanjan; Mukherjee, Shibabrata; Ghosh, Susmita; Kumar, Shishir; Sarkar, Kumkum; Pal, Dipankar; Bhowmik, Pratik; Mandal, Kausik; Modak, Dolanchampa; Guha, Subhasish Kamal; Pramanik, Netai; Goswami, Rama Prosad; Saha, Bibhuti; Chatterjee, Mitali

doi:10.1007/s10875-014-0115-3

Cited by 21 publications

(26 citation statements)

References 48 publications

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“…The plasma levels of proinflammatory (IFN‐γ, IL‐1β, IL‐6, IL‐8, TNF‐α), anti‐inflammatory (IL‐4, IL‐13) and counter‐regulatory (IL‐10) cytokines were measured. Except for IL‐1β and IL‐6, there was a significant enhancement of other proinflammatory cytokines (Table ), corroborating with previous studies . Furthermore, the proinflammatory cytokines, IFN‐γ, IL‐8 and TNF‐α, correlated positively with parasite load, r values being .45, .86 and .58, respectively (Table ).…”

Section: Resultssupporting

confidence: 89%

“…With regard to human infectious diseases, patients with PKDL demonstrated a mixed profile of M(IL‐4) and M(IL‐10) . In patients with VL, a mixed Th1/Th2 response of cytokines included increased levels of Th1 cytokines, IFN‐γ, IL‐8, TNF‐α and Th2 cytokines, IL‐4 and IL‐10 and our study was in concordance (Table ). What was of biological relevance was that these cytokines correlated positively with parasite load, substantiating disease specificity (Table ).…”

Section: Discussionsupporting

confidence: 85%

“…The frequency of surface markers on monocytes was evaluated by immunophenotyping using whole blood (100 μL) that was stained with antihuman CD64 PE, CD32 APC, CD210 PE, CD14 FITC, CD206 PE or CD163 PE as previously described …”

Section: Methodsmentioning

confidence: 99%

“…Peripheral blood was layered over Histopaque and intracellular IL‐10 or LAP‐TGFβ1 detected as previously described …”

Section: Methodsmentioning

confidence: 99%

“…To overcome the potent armamentarium of monocytes/macrophages, Leishmania adopts several strategies that include modulation of their redox status, which along with impaired antigen presentation, collectively favours parasite survival . Depending on the immediate microenvironment, macrophages can be polarized towards classical or alternative activation, and accordingly perform biological roles that range from inducers to regulators and effectors of innate as also acquired immunity …”

Section: Introductionmentioning

confidence: 99%

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

Roy

Mukhopadhyay

Mukherjee

et al. 2018

Parasite Immunology

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Leishmania donovani, the causative parasite of Visceral Leishmaniasis (VL), deviously manipulates host monocytes/macrophages to ensure its survival. Although monocytes/macrophages from patients with VL have demonstrated an impaired oxidative burst and antigen presentation, an unanswered yet pertinent question remains as to whether they are deactivated or alternatively activated. The significantly raised plasma levels of IL-4/IL-13 and IL-10 in VL patients suggested a microenvironment conducive for alternative activation of monocytes/macrophages. Accordingly, the classical markers for IL-4-driven monocytes/macrophages [M(IL-4)] were studied namely intramonocytic CD206 , circulating CCL22 and CCL17, and were unchanged. Furthermore, the mRNA expression of Kruppel-like factor 4 (KLF4), peroxisome proliferator-activated receptors (PPAR)-γ and arginase-I (ARG-I) in peripheral blood mononuclear cells was unaltered. However, markers for IL-10-driven monocytes/macrophages [M(IL-10)], namely soluble CD163, intramonocytic IL-10, and circulating CXCL13 were significantly increased. Monocytes/macrophages of patients with VL demonstrated an increased expression of markers for M(IL-10), along with the absence of markers for M(IL-4). Taken together, in human VL, manipulation of these IL-10 polarized monocytes-macrophages may pave the way for improved therapeutic outcomes.

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Section: Resultssupporting

confidence: 89%

Section: Discussionsupporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

“…Peripheral blood was layered over Histopaque and intracellular IL‐10 or LAP‐TGFβ1 detected as previously described …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Roy

Mukhopadhyay

Mukherjee

et al. 2018

Parasite Immunology

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Revisiting the Principles of Designing a Vaccine

et al. 2021

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Immune principles formulated by Jenner, Pasteur, and early immunologists served as fundamental propositions for vaccine discovery against many dreadful pathogens. However, decisive success in the form of an efficacious vaccine still eludes for diseases such as tuberculosis, leishmaniasis, and trypanosomiasis. Several antileishmanial vaccine trials have been undertaken in past decades incorporating live, attenuated, killed, or subunit vaccination, but the goal remains unmet. In light of the above facts, we have to reassess the principles of vaccination by dissecting factors associated with the hosts' immune response. This chapter discusses the pathogen-associated perturbations at various junctures during the generation of the immune response which inhibits antigenic processing, presentation, or remodels memory T cell repertoire. This can lead to ineffective priming or inappropriate activation of memory T cells during challenge infection. Thus, despite a protective primary response, vaccine failure can occur due to altered immune environments in the presence of pathogens.

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New Approaches to Evaluate the Cytotoxic Potential of Leishmanicidal Drugs Using Human Peripheral Blood

Teixeira-Carvalho

Cota

Murta

et al. 2022

Biomarkers in Toxicology

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

Abstract: 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.

Cited by 21 publications

References 48 publications

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

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

Revisiting the Principles of Designing a Vaccine

New Approaches to Evaluate the Cytotoxic Potential of Leishmanicidal Drugs Using Human Peripheral Blood

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