Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes induce in vivo leukocyte recruitment dependent on MCP-1 production by IFN-gamma-primed-macrophages.
Glycosylphosphatidylinositol-anchored mucin-like glycoproteins from Trypanosoma cruzi trypomastigotes (tGPI-mucins) activate macrophages in vitro to produce proinflammatory cytokines, chemokines, and nitric oxide. These effects of tGPI-mucins may be important in the ensuing immune response to T. cruzi. Here, we have sought evidence for a role of tGPI-mucins in mediating leukocyte recruitment in vivo. tGPI-mucins are highly effective in promoting cell recruitment in the pleural cavity of mice primed with IFN-gamma-inducing agents but not in naïve mice. Maximal recruitment was observed at a dose between 250 and 1250 ng tGPI-mucins. There was a significant elevation in the levels of MCP-1 in the pleural cavity of primed animals injected with tGPI-mucins, and in vivo neutralization of MCP-1 abolished leukocyte recruitment. Pretreatment with anti-MIP-1alpha or anti-RANTES had no effect on the recruitment induced by tGPI-mucins. MCP-1 immunoreactivity was detected in pleural macrophages, and macrophages produced MCP-1 in vitro, especially after priming with IFN-gamma. Finally, tGPI-mucins induced significant leukocyte recruitment in primed C3H/HeJ but not in TLR2-deficient mice. Together, our results suggest that T. cruzi-derived GPI-mucins in conjunction with IFN-gamma may drive tissue chemokine production and inflammation and bear a significant role in the pathogenesis of Chagas disease.
Coelho
Patrícia S
PS
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627-Pampulha, 31270-901 Belo Horizonte, MG, Brazil.
Klein
André
A
Talvani
André
A
Coutinho
Sibele F
SF
Takeuchi
Osamu
O
Akira
Shizuo
S
Silva
João S
JS
Canizzaro
Hélia
H
Gazzinelli
Ricardo T
RT
Teixeira
Mauro M
MM
D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D018925:Chemokines / Q000235:genetics / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D029721:Drosophila Proteins; D017261:Glycosylphosphatidylinositols / Q000032:analysis; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D009077:Mucins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000502:physiology; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014349:Trypanosoma cruzi / Q000254:growth & development / Q000502:physiology*
D018932:Chemokine CCL2; D018925:Chemokines; D029721:Drosophila Proteins; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D009077:Mucins; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D007371:Interferon-gamma