title: Foxp3 and IL-10 expression correlates with parasite burden in lesional tissues of post kala azar dermal leishmaniasis (PKDL) patients.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.
authors.forename: Gajendra Kumar
authors.initials: GK
authors.lastname: Katara
authors.forename: Nasim Akhtar
authors.initials: NA
authors.lastname: Ansari
authors.forename: Sandeep
authors.initials: S
authors.lastname: Verma
authors.forename: V
authors.initials: V
authors.lastname: Ramesh
authors.forename: Poonam
authors.initials: P
authors.lastname: Salotra
mesh_terms: D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D060908:CTLA-4 Antigen; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D020869:Gene Expression Profiling; D006801:Humans; D016753:Interleukin-10 / Q000032:analysis*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D007893:Leishmania donovani / Q000302:isolation & purification*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D007898:Leishmaniasis, Visceral / Q000150:complications*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012867:Skin / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D016753:Interleukin-10