Filarial lymphedema is characterized by antigen-specific Th1 and Th17 proinflammatory responses and a lack of regulatory T cells

Subash Babu, Sajid Q. Bhat, N. Pavan Kumar, Angelo Lipira, Sanath Kumar, C. Karthik, V. Kumaraswami, Thomas B. Nutman

Research output: Contribution to journalArticle

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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-γ and TNF-α - 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, TGFb, 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.

Original languageEnglish (US)
Article numbere420
JournalPLoS neglected tropical diseases
Volume3
Issue number4
DOIs
StatePublished - May 19 2009
Externally publishedYes

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Lymphedema
Regulatory T-Lymphocytes
Antigens
Interleukin-17
Cytokines
Toll-Like Receptor 10
Elephantiasis
Filarial Elephantiasis
Pathology
Interleukin-23
Toll-Like Receptors
T-Lymphocyte Subsets
Parasites
Messenger RNA

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Filarial lymphedema is characterized by antigen-specific Th1 and Th17 proinflammatory responses and a lack of regulatory T cells. / Babu, Subash; Bhat, Sajid Q.; Kumar, N. Pavan; Lipira, Angelo; Kumar, Sanath; Karthik, C.; Kumaraswami, V.; Nutman, Thomas B.

In: PLoS neglected tropical diseases, Vol. 3, No. 4, e420, 19.05.2009.

Research output: Contribution to journalArticle

Babu, Subash ; Bhat, Sajid Q. ; Kumar, N. Pavan ; Lipira, Angelo ; Kumar, Sanath ; Karthik, C. ; Kumaraswami, V. ; Nutman, Thomas B. / Filarial lymphedema is characterized by antigen-specific Th1 and Th17 proinflammatory responses and a lack of regulatory T cells. In: PLoS neglected tropical diseases. 2009 ; Vol. 3, No. 4.
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