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

Katara GK, Ansari NA, Verma S, Ramesh V, Salotra P - PLoS Negl Trop Dis (2011)

Bottom Line: 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.Further, Foxp3, CD25 and IL-10 mRNA levels directly correlated with parasite load in lesions tissues.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.

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.

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Related in: MedlinePlus

Ex vivo analysis of mRNA expression of Treg markers and IL-10 in PKDL.Relative mRNA levels of CD25, Foxp3, CTLA-4 and IL-10 in lesion tissues of PKDL patients determined by real time polymerase chain reaction at pretreatment (n = 25) or post treatment (n = 8), or control tissues (n = 5) (A) and in paired samples (n = 8) shown separately (B). **P<0.01, and ***P<0.001.
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pntd-0001171-g001: Ex vivo analysis of mRNA expression of Treg markers and IL-10 in PKDL.Relative mRNA levels of CD25, Foxp3, CTLA-4 and IL-10 in lesion tissues of PKDL patients determined by real time polymerase chain reaction at pretreatment (n = 25) or post treatment (n = 8), or control tissues (n = 5) (A) and in paired samples (n = 8) shown separately (B). **P<0.01, and ***P<0.001.

Mentions: Natural Treg markers and IL-10 mRNA level were evaluated in skin lesion tissues of PKDL patients and compared with healthy controls tissues. mRNA analysis showed significantly elevated levels of nTreg markers in pre-treatment cases compared to control (Foxp3, P = 0.0009; CD25 & CTLA-4, P<0.0001) (Figure 1A). After treatment, a significant decrement in mRNA levels (Foxp3, P = 0.0025; CD25, P = 0.0002 & CTLA-4, P<0.0001) was noticed in paired samples (Figure 1B). In addition, we evaluated mRNA levels of IL-10, a molecule produced by adaptive Treg or Tr1 cells, and frequently associated with experimental or human VL pathology [5]–[7]. IL-10 mRNA level was significantly elevated in PKDL compared to control (P<0.0001). A significant drop in IL-10 mRNA levels was noticed in paired samples (P = 0.0004) (Figure 1).


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

Katara GK, Ansari NA, Verma S, Ramesh V, Salotra P - PLoS Negl Trop Dis (2011)

Ex vivo analysis of mRNA expression of Treg markers and IL-10 in PKDL.Relative mRNA levels of CD25, Foxp3, CTLA-4 and IL-10 in lesion tissues of PKDL patients determined by real time polymerase chain reaction at pretreatment (n = 25) or post treatment (n = 8), or control tissues (n = 5) (A) and in paired samples (n = 8) shown separately (B). **P<0.01, and ***P<0.001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3104974&req=5

pntd-0001171-g001: Ex vivo analysis of mRNA expression of Treg markers and IL-10 in PKDL.Relative mRNA levels of CD25, Foxp3, CTLA-4 and IL-10 in lesion tissues of PKDL patients determined by real time polymerase chain reaction at pretreatment (n = 25) or post treatment (n = 8), or control tissues (n = 5) (A) and in paired samples (n = 8) shown separately (B). **P<0.01, and ***P<0.001.
Mentions: Natural Treg markers and IL-10 mRNA level were evaluated in skin lesion tissues of PKDL patients and compared with healthy controls tissues. mRNA analysis showed significantly elevated levels of nTreg markers in pre-treatment cases compared to control (Foxp3, P = 0.0009; CD25 & CTLA-4, P<0.0001) (Figure 1A). After treatment, a significant decrement in mRNA levels (Foxp3, P = 0.0025; CD25, P = 0.0002 & CTLA-4, P<0.0001) was noticed in paired samples (Figure 1B). In addition, we evaluated mRNA levels of IL-10, a molecule produced by adaptive Treg or Tr1 cells, and frequently associated with experimental or human VL pathology [5]–[7]. IL-10 mRNA level was significantly elevated in PKDL compared to control (P<0.0001). A significant drop in IL-10 mRNA levels was noticed in paired samples (P = 0.0004) (Figure 1).

Bottom Line: 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.Further, Foxp3, CD25 and IL-10 mRNA levels directly correlated with parasite load in lesions tissues.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.

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.

Show MeSH
Related in: MedlinePlus