Toll-like receptor 4 (TLR4)-dependent proinflammatory and immunomodulatory properties of the glycoinositolphospholipid (GIPL) from Trypanosoma cruzi.
We have demonstrated recently that the glycoinositolphospholipid (GIPL) molecule from the protozoan Trypanosoma cruzi is a TLR4 agonist with proinflammatory effects. Here, we show that GIPL-induced neutrophil recruitment into the peritoneal cavity is mediated by at least two pathways: one, where IL-1beta acts downstream of TNF-alpha, and a second, which is IL-1beta- and TNFRI-independent. Moreover, NKT cells participate in this proinflammatory cascade, as in GIPL-treated CD1d(-/-) mice, TNF-alpha and MIP-2 levels are reduced significantly. As a consequence of this inflammatory response, spleen and lymph nodes of GIPL-treated mice have an increase in the percentage of T and B cells expressing the CD69 activation marker. Cell-transfer experiments demonstrate that T and B cell activation by GIPL is an indirect effect, which relies on the expression of TLR4 by other cell types. Moreover, although signaling through TNFRI contributes to the activation of B and gammadelta+ T cells, it is not required for increasing CD69 expression on alphabeta+ T lymphocytes. It is interesting that T cells are also functionally affected by GIPL treatment, as spleen cells from GIPL-injected mice show enhanced production of IL-4 following in vitro stimulation by anti-CD3. Together, these results contribute to the understanding of the inflammatory properties of the GIPL molecule, pointing to its potential role as a parasite-derived modulator of the immune response during T. cruzi infection.
Medeiros
Monica M
MM
Instituto de Microbiologia Prof. Paulo de Góes, Universidade Federal do Rio de Janeiro, CCS Bloco I, 20 andar Sala: I2-051, Avenida Carlos Chagas Filho, 373, Cidade Universitária, Ilha do Fundão, CEP: 21941-902, Rio de Janeiro, RJ, Brazil.
Peixoto
Jaqueline R
JR
Oliveira
Ana-Carolina
AC
Cardilo-Reis
Larissa
L
Koatz
Vera L G
VL
Van Kaer
Luc
L
Previato
José O
JO
Mendonça-Previato
Lúcia
L
Nobrega
Alberto
A
Bellio
Maria
M
D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000502:physiology; D055610:Antigens, CD1d; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006017:Glycolipids / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D007113:Immunity, Innate / Q000235:genetics; D018836:Inflammation Mediators / Q000502:physiology*; D053583:Interleukin-1beta / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D010743:Phospholipids / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018949:Antigens, CD1; D055610:Antigens, CD1d; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D006017:Glycolipids; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D010743:Phospholipids; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C115336:glycoinositolphospholipid, Trypanosoma