Foxp3 and IL-10 expression correlates with parasite burden in lesional tissues of post kala azar dermal leishmaniasis (PKDL) patients

PLoS Negl Trop Dis. 2011;5(5):e1171. doi: 10.1371/journal.pntd.0001171. Epub 2011 May 31.

Abstract

Background: Post 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 findings: Present 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/significance: Data 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antigens, CD / analysis
  • CTLA-4 Antigen
  • Female
  • Forkhead Transcription Factors / analysis*
  • Gene Expression Profiling
  • Humans
  • Interleukin-10 / analysis*
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Leishmania donovani / isolation & purification*
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / parasitology
  • Leishmaniasis, Visceral / complications*
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Skin / immunology*
  • Skin / pathology
  • T-Lymphocytes, Regulatory / chemistry
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Antigens, CD
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL10 protein, human
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • RNA, Messenger
  • Interleukin-10