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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

Correlation of mRNA expression of Treg markers and IL-10 with parasite load in PKDL.Relative mRNA levels of Treg markers and IL-10 with respect to parasite load within lesion tissues of PKDL patients (n = 15). Plot was created using logarithmic values for cycles over 18sRNA and parasite load. Correlation was calculated using Spearman/Pearson correlation test. Diagonal line represents linear regression.
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pntd-0001171-g002: Correlation of mRNA expression of Treg markers and IL-10 with parasite load in PKDL.Relative mRNA levels of Treg markers and IL-10 with respect to parasite load within lesion tissues of PKDL patients (n = 15). Plot was created using logarithmic values for cycles over 18sRNA and parasite load. Correlation was calculated using Spearman/Pearson correlation test. Diagonal line represents linear regression.

Mentions: To further evaluate whether there is any direct association between expression of these molecules and parasite burden, we evaluated the parasite load in PKDL lesion tissues (n = 15). The median parasite load was 776 parasites/µg tissue DNA (range = 3 to 590,000 parasites/µg tissue DNA), with a higher parasite load in nodular lesions (median 2,244 parasites/µg tissue DNA, n = 10) as compared to that in papular/macular lesions (median 28 parasites/µg tissue DNA, n = 5). Ex vivo analysis showed a direct correlation between parasite load and mRNA levels in lesion tissues (CD25, r = 0.691; Foxp3, r = 0.817; IL-10, r = 0.821), such correlation was not noticed for CTLA-4 (Figure 2). No parasite was detected in any of the post treatment sample.


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)

Correlation of mRNA expression of Treg markers and IL-10 with parasite load in PKDL.Relative mRNA levels of Treg markers and IL-10 with respect to parasite load within lesion tissues of PKDL patients (n = 15). Plot was created using logarithmic values for cycles over 18sRNA and parasite load. Correlation was calculated using Spearman/Pearson correlation test. Diagonal line represents linear regression.
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0001171-g002: Correlation of mRNA expression of Treg markers and IL-10 with parasite load in PKDL.Relative mRNA levels of Treg markers and IL-10 with respect to parasite load within lesion tissues of PKDL patients (n = 15). Plot was created using logarithmic values for cycles over 18sRNA and parasite load. Correlation was calculated using Spearman/Pearson correlation test. Diagonal line represents linear regression.
Mentions: To further evaluate whether there is any direct association between expression of these molecules and parasite burden, we evaluated the parasite load in PKDL lesion tissues (n = 15). The median parasite load was 776 parasites/µg tissue DNA (range = 3 to 590,000 parasites/µg tissue DNA), with a higher parasite load in nodular lesions (median 2,244 parasites/µg tissue DNA, n = 10) as compared to that in papular/macular lesions (median 28 parasites/µg tissue DNA, n = 5). Ex vivo analysis showed a direct correlation between parasite load and mRNA levels in lesion tissues (CD25, r = 0.691; Foxp3, r = 0.817; IL-10, r = 0.821), such correlation was not noticed for CTLA-4 (Figure 2). No parasite was detected in any of the post treatment sample.

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