Setaria digitata secreted filarial lipids modulate IL-12 signaling through JAK-STAT pathway leading to the development of Th1 response.
Filariasis is a debilitating parasitic disease in many tropical countries. Despite the highly evolved immune system, the filarial parasites successfully evade host immunity to persist for a sustained period of time. Earlier studies have shown that the filarial parasites achieve this long-term survival through release of immunosuppressive materials in the host. In this study, we show that the secreted filarial lipids (SFL) isolated from Setaria digitata suppress Th1 immune response. While immunization with myelin antigen induces Th1 response in mice, in vitro treatment with SFL resulted in a dose-dependent decrease in myelin antigen-induced proliferation and secretion of IL-12 and IFNgamma. The SFL also inhibited IL-12-induced T cell proliferation and Th1 differentiation in vitro. The inhibition of T cell responses by SFL associates with the blockade of IL-12-induced activation of JAK-STAT signaling pathway in T cells. These findings suggest that the SFL modulates Th1 immune response by blocking IL-12 signaling in T cells and thus play a role in host immune evasion of filarial parasites.
Muthian
Gladson
G
Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
Pradeep
Chellappan G
CG
Sargapradeep
Kuttappan
K
Kaleysaraj
Raghavan
R
Bright
John J
JJ
D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D047468:Immunoprecipitation; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis / Q000276:immunology* / Q000502:physiology; D053612:Janus Kinases / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D050791:STAT Transcription Factors / Q000502:physiology; D017182:Setaria Nematode / Q000276:immunology* / Q000378:metabolism; D012719:Setariasis / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D008055:Lipids; C571327:Mog protein, mouse; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D050791:STAT Transcription Factors; D018664:Interleukin-12; D007371:Interferon-gamma; D053612:Janus Kinases