Abstract
BackgroundPost kala-azar dermal leishmaniasis (PKDL), a sequel to visceral leishamaniasis (VL) in 5–15% cases, constitutes a parasite reservoir important in disease transmission. The precise immunological cause of PKDL outcome remains obscure. However, overlapping counter regulatory responses with elevated IFN-γ and IL-10 are reported.Methodology/Principal FindingsPresent study deals with ex-vivo mRNA and protein analysis of natural regulatory T cells (nTreg) markers (Foxp3, CD25 and CTLA-4) and IL-10 levels in lesion tissues of PKDL patients at pre and post treatment stages. In addition, correlation of nTreg markers and IL-10 with parasite load in tissue lesions was investigated. mRNA levels of nTreg markers and IL-10 were found significantly elevated in pre-treatment PKDL cases compared to controls (Foxp3, P = 0.0009; CD25 & CTLA-4, P<0.0001; IL-10, P<0.0001), and were restored after treatment. Analysis of nTreg cell markers and IL-10 in different clinical manifestations of disease revealed elevated levels in nodular lesions compared to macules/papules. Further, Foxp3, CD25 and IL-10 mRNA levels directly correlated with parasite load in lesions tissues.Conclusion/SignificanceData demonstrated accumulation of nTreg cells in infected tissue and a correlation of both IL-10 and nTreg levels with parasite burden suggesting their role in disease severity in PKDL.
Highlights
Leishmaniasis constitutes various forms of globally widespread group of neglected diseases caused by an obligatory intracellular protozoan parasite of genus Leishmania
Post kala azar dermal leishamniasis (PKDL), an unusual dermatosis develops in 5–15% of apparently cured visceral leishmaniasis cases in India and in about 60% of cases in Sudan
In this study we reported the accumulation of natural regulatory T cells (nTreg) cells in lesion tissues of Post kala-azar dermal leishmaniasis (PKDL) patients
Summary
Leishmaniasis constitutes various forms of globally widespread group of neglected diseases caused by an obligatory intracellular protozoan parasite of genus Leishmania. It is currently endemic in 88 countries and overall prevalence is estimated as 12 million with 350 million at risk. PKDL is an unusual dermatosis that develops in 5–15% of apparently cured VL cases in India and in about 60% of cases in Sudan [2] This chronic skin condition produces gross cutaneous lesions in the form of hypopigmented macules, erythema and nodular stages. Post kala-azar dermal leishmaniasis (PKDL), a sequel to visceral leishamaniasis (VL) in 5–15% cases, constitutes a parasite reservoir important in disease transmission. Overlapping counter regulatory responses with elevated IFN-c and IL-10 are reported
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