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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

Immunohistochemical analysis of Foxp3 in tissue lesions of PKDL patients.Distribution of Foxp3 in dermal lesion tissue sections at pre treatment, post treatment stages and normal skin of healthy individuals. Panel A (10×), Panel B (40×) magnification.
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pntd-0001171-g003: Immunohistochemical analysis of Foxp3 in tissue lesions of PKDL patients.Distribution of Foxp3 in dermal lesion tissue sections at pre treatment, post treatment stages and normal skin of healthy individuals. Panel A (10×), Panel B (40×) magnification.

Mentions: To authenticate mRNA expression at protein level, IHC staining for Foxp3 expression was evaluated between groups. Three PKDL samples showed intense nuclear staining for Foxp3 in tissue infiltrate region. After treatment there was a substantial reduction in Foxp3+ cells and cell infiltrates. Representative examples are illustrated in Figure 3.


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)

Immunohistochemical analysis of Foxp3 in tissue lesions of PKDL patients.Distribution of Foxp3 in dermal lesion tissue sections at pre treatment, post treatment stages and normal skin of healthy individuals. Panel A (10×), Panel B (40×) magnification.
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0001171-g003: Immunohistochemical analysis of Foxp3 in tissue lesions of PKDL patients.Distribution of Foxp3 in dermal lesion tissue sections at pre treatment, post treatment stages and normal skin of healthy individuals. Panel A (10×), Panel B (40×) magnification.
Mentions: To authenticate mRNA expression at protein level, IHC staining for Foxp3 expression was evaluated between groups. Three PKDL samples showed intense nuclear staining for Foxp3 in tissue infiltrate region. After treatment there was a substantial reduction in Foxp3+ cells and cell infiltrates. Representative examples are illustrated in Figure 3.

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