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Filarial lymphedema is characterized by antigen-specific Th1 and th17 proinflammatory responses and a lack of regulatory T cells.

Babu S, Bhat SQ, Pavan Kumar N, Lipira AB, Kumar S, Karthik C, Kumaraswami V, Nutman TB - PLoS Negl Trop Dis (2009)

Bottom Line: We also examined expression patterns of Toll-like receptors (TLR1-10) and Nod-like receptors (Nod1, Nod2, and NALP3) in response to BmA.BmA induced significantly higher production of Th1-type cytokines-IFN-gamma and TNF-alpha-in patients with lymphedema compared with asymptomatic individuals.Our findings implicate increased Th1/Th17 responses and decreased regulatory T cells as well as regulation of Toll- and Nod-like receptors in pathogenesis of filarial lymphedema.

View Article: PubMed Central - PubMed

Affiliation: National Institutes of Health-International Center for Excellence in Research, Chennai, India. sbabu@mail.nih.gov

ABSTRACT

Background: Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients.

Methods and findings: To elucidate the role of CD4(+) T cell subsets in the development of lymphatic pathology, we examined specific sets of cytokines in individuals with filarial lymphedema in response to parasite antigen (BmA) and compared them with responses from asymptomatic infected individuals. We also examined expression patterns of Toll-like receptors (TLR1-10) and Nod-like receptors (Nod1, Nod2, and NALP3) in response to BmA. BmA induced significantly higher production of Th1-type cytokines-IFN-gamma and TNF-alpha-in patients with lymphedema compared with asymptomatic individuals. Notably, expression of the Th17 family of cytokines-IL-17A, IL-17F, IL-21, and IL-23-was also significantly upregulated by BmA stimulation in lymphedema patients. In contrast, expression of Foxp3, GITR, TGFbeta, and CTLA-4, known to be expressed by regulatory T cells, was significantly impaired in patients with lymphedema. BmA also induced significantly higher expression of TLR2, 4, 7, and 9 as well Nod1 and 2 mRNA in patients with lymphedema compared with asymptomatic controls.

Conclusion: Our findings implicate increased Th1/Th17 responses and decreased regulatory T cells as well as regulation of Toll- and Nod-like receptors in pathogenesis of filarial lymphedema.

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Related in: MedlinePlus

Filarial lymphedema is associated with increased expression of TLR2, 4, 7 and 9 mRNA.PBMCs from filarial lymphedema [CP] (n = 12) and asymptomatic infected [INF] (n = 10) patients were stimulated with BmA (10 µg/ml) for 24 hours, and TLR1-10 mRNA were measured by real-time RT-PCR. Results are shown as fold change over media control. P values were calculated using the Mann-Whitney test.
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pntd-0000420-g005: Filarial lymphedema is associated with increased expression of TLR2, 4, 7 and 9 mRNA.PBMCs from filarial lymphedema [CP] (n = 12) and asymptomatic infected [INF] (n = 10) patients were stimulated with BmA (10 µg/ml) for 24 hours, and TLR1-10 mRNA were measured by real-time RT-PCR. Results are shown as fold change over media control. P values were calculated using the Mann-Whitney test.

Mentions: Because TLR have been implicated in development of pathology in animal models of filarial parasites as well as in a related filarial infection, onchocerciasis [4], we sought to determine the role of TLR expression in development of filarial lymphedema by examining the expression patterns of all ten human TLRs in PBMCs of CP and INF patients following 24-hour stimulation with BmA or PPD. As shown in Figure 5, CP exhibit significantly higher induction of BmA-stimulated TLR2 (GM fold change of 1.470 vs. 0.7357; P = 0.0068), TLR4 (GM fold change of 1.146 vs. 0.5216; P = 0.0176), TLR7 (GM fold change of 1.049 vs. 0.4361; P = 0.0377) and TLR9 (GM fold change of 1.217 vs. 0.6622; P = 0.0377) expression in comparison with INF. No significant alteration in the expression of other TLRs was observed in response to BmA (Figure 5). No significant difference in the expression levels of TLRs was observed in response to PPD stimulation (data not shown).


Filarial lymphedema is characterized by antigen-specific Th1 and th17 proinflammatory responses and a lack of regulatory T cells.

Babu S, Bhat SQ, Pavan Kumar N, Lipira AB, Kumar S, Karthik C, Kumaraswami V, Nutman TB - PLoS Negl Trop Dis (2009)

Filarial lymphedema is associated with increased expression of TLR2, 4, 7 and 9 mRNA.PBMCs from filarial lymphedema [CP] (n = 12) and asymptomatic infected [INF] (n = 10) patients were stimulated with BmA (10 µg/ml) for 24 hours, and TLR1-10 mRNA were measured by real-time RT-PCR. Results are shown as fold change over media control. P values were calculated using the Mann-Whitney test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2666805&req=5

pntd-0000420-g005: Filarial lymphedema is associated with increased expression of TLR2, 4, 7 and 9 mRNA.PBMCs from filarial lymphedema [CP] (n = 12) and asymptomatic infected [INF] (n = 10) patients were stimulated with BmA (10 µg/ml) for 24 hours, and TLR1-10 mRNA were measured by real-time RT-PCR. Results are shown as fold change over media control. P values were calculated using the Mann-Whitney test.
Mentions: Because TLR have been implicated in development of pathology in animal models of filarial parasites as well as in a related filarial infection, onchocerciasis [4], we sought to determine the role of TLR expression in development of filarial lymphedema by examining the expression patterns of all ten human TLRs in PBMCs of CP and INF patients following 24-hour stimulation with BmA or PPD. As shown in Figure 5, CP exhibit significantly higher induction of BmA-stimulated TLR2 (GM fold change of 1.470 vs. 0.7357; P = 0.0068), TLR4 (GM fold change of 1.146 vs. 0.5216; P = 0.0176), TLR7 (GM fold change of 1.049 vs. 0.4361; P = 0.0377) and TLR9 (GM fold change of 1.217 vs. 0.6622; P = 0.0377) expression in comparison with INF. No significant alteration in the expression of other TLRs was observed in response to BmA (Figure 5). No significant difference in the expression levels of TLRs was observed in response to PPD stimulation (data not shown).

Bottom Line: We also examined expression patterns of Toll-like receptors (TLR1-10) and Nod-like receptors (Nod1, Nod2, and NALP3) in response to BmA.BmA induced significantly higher production of Th1-type cytokines-IFN-gamma and TNF-alpha-in patients with lymphedema compared with asymptomatic individuals.Our findings implicate increased Th1/Th17 responses and decreased regulatory T cells as well as regulation of Toll- and Nod-like receptors in pathogenesis of filarial lymphedema.

View Article: PubMed Central - PubMed

Affiliation: National Institutes of Health-International Center for Excellence in Research, Chennai, India. sbabu@mail.nih.gov

ABSTRACT

Background: Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients.

Methods and findings: To elucidate the role of CD4(+) T cell subsets in the development of lymphatic pathology, we examined specific sets of cytokines in individuals with filarial lymphedema in response to parasite antigen (BmA) and compared them with responses from asymptomatic infected individuals. We also examined expression patterns of Toll-like receptors (TLR1-10) and Nod-like receptors (Nod1, Nod2, and NALP3) in response to BmA. BmA induced significantly higher production of Th1-type cytokines-IFN-gamma and TNF-alpha-in patients with lymphedema compared with asymptomatic individuals. Notably, expression of the Th17 family of cytokines-IL-17A, IL-17F, IL-21, and IL-23-was also significantly upregulated by BmA stimulation in lymphedema patients. In contrast, expression of Foxp3, GITR, TGFbeta, and CTLA-4, known to be expressed by regulatory T cells, was significantly impaired in patients with lymphedema. BmA also induced significantly higher expression of TLR2, 4, 7, and 9 as well Nod1 and 2 mRNA in patients with lymphedema compared with asymptomatic controls.

Conclusion: Our findings implicate increased Th1/Th17 responses and decreased regulatory T cells as well as regulation of Toll- and Nod-like receptors in pathogenesis of filarial lymphedema.

Show MeSH
Related in: MedlinePlus