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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 elevated Th1 cytokine secretion.(A, B) PBMCs from filarial lymphedema [CP] (n = 12) and asymptomatic infected [INF] (n = 10) patients stimulated with (A) BmA (10 µg/ml) or (B) PPD (10 µg/ml) for 24 hours, and Th1 - IL-2, IFN-γ, and TNF-α cytokine levels were measured by ELISA. Results are shown as net cytokine production over media control. P values were calculated using the Mann-Whitney test.
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pntd-0000420-g001: Filarial lymphedema is associated with elevated Th1 cytokine secretion.(A, B) PBMCs from filarial lymphedema [CP] (n = 12) and asymptomatic infected [INF] (n = 10) patients stimulated with (A) BmA (10 µg/ml) or (B) PPD (10 µg/ml) for 24 hours, and Th1 - IL-2, IFN-γ, and TNF-α cytokine levels were measured by ELISA. Results are shown as net cytokine production over media control. P values were calculated using the Mann-Whitney test.

Mentions: To determine the role of Th1 cytokines in development of lymphedema, we stimulated PBMCs from CP and INF patients with BmA or PPD for 24 hours and measured the levels of prototypical Th1 cytokines by ELISA. As shown in Figure 1A, BmA induced significantly increased production of IFN-γ (geometric mean [GM] of 956.8 pg/ml in CP vs. 24.88 pg/ml in INF; P<0.0001) and TNF-α (GM of 200.2 vs. 25.64; P = 0.0033) but not IL-2 (GM of 501.5 vs. 308.5) in CP compared with INF. As shown in Figure 1B, no significant alteration in the production of IFN-γ (GM of 659.1 vs. 707.7), TNF-α (GM of 185.0 vs. 428.5), and IL-2 (GM of 296.5 vs. 210.8) was observed in response to the control antigen PPD. Thus, elevated Th1 responses in CP patients were filarial-antigen specific.


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 elevated Th1 cytokine secretion.(A, B) PBMCs from filarial lymphedema [CP] (n = 12) and asymptomatic infected [INF] (n = 10) patients stimulated with (A) BmA (10 µg/ml) or (B) PPD (10 µg/ml) for 24 hours, and Th1 - IL-2, IFN-γ, and TNF-α cytokine levels were measured by ELISA. Results are shown as net cytokine production 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-g001: Filarial lymphedema is associated with elevated Th1 cytokine secretion.(A, B) PBMCs from filarial lymphedema [CP] (n = 12) and asymptomatic infected [INF] (n = 10) patients stimulated with (A) BmA (10 µg/ml) or (B) PPD (10 µg/ml) for 24 hours, and Th1 - IL-2, IFN-γ, and TNF-α cytokine levels were measured by ELISA. Results are shown as net cytokine production over media control. P values were calculated using the Mann-Whitney test.
Mentions: To determine the role of Th1 cytokines in development of lymphedema, we stimulated PBMCs from CP and INF patients with BmA or PPD for 24 hours and measured the levels of prototypical Th1 cytokines by ELISA. As shown in Figure 1A, BmA induced significantly increased production of IFN-γ (geometric mean [GM] of 956.8 pg/ml in CP vs. 24.88 pg/ml in INF; P<0.0001) and TNF-α (GM of 200.2 vs. 25.64; P = 0.0033) but not IL-2 (GM of 501.5 vs. 308.5) in CP compared with INF. As shown in Figure 1B, no significant alteration in the production of IFN-γ (GM of 659.1 vs. 707.7), TNF-α (GM of 185.0 vs. 428.5), and IL-2 (GM of 296.5 vs. 210.8) was observed in response to the control antigen PPD. Thus, elevated Th1 responses in CP patients were filarial-antigen specific.

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