Eotaxin-1-regulated eosinophils have a critical role in innate immunity against experimental Brugia malayi infection.
Using two models of filarial infection in which Brugia malayi microfilariae (Mf) are contained in distinct anatomical compartments, in blood or tissue sites, we have demonstrated a critical role for eotaxin-1 in parasite clearance. In the first model, implantation of adult B. malayi into the peritoneal cavity of eotaxin-1(-/-) mice resulted in increased Mf survival associated with a dramatic reduction in peritoneal cavity eosinophilic infiltration. In the second model Mf were injected intravenously into eotaxin-1(-/-) mice; Mf clearance from the blood was more rapid than in wild-type mice and was associated with a pronounced blood eosinophilia, resulting from the inability of eosinophils to migrate to tissue sites in the absence of eotaxin-1. (Eotaxin-1 + IL-5)(-/-) mice had extended Mf survival in the blood and significantly reduced blood eosinophil levels. Interestingly, rapid clearance of a secondary Mf infection following immunization was unaltered in either eotaxin-1(-/-) mice or (eotaxin-1 + IL-5)(-/-) mice. Eosinophil peroxidase levels were high during primary, but not secondary infection, suggesting that eosinophil degranulation is important during primary Mf clearance. Thus, our data show that the presence of eosinophils is critical for innate clearance of B. malayi Mf infection, whereas rapid clearance of secondary infections is independent of both eotaxin-1 and IL-5.
Simons
Jonathan E
JE
School of Biological Sciences, University of Manchester, Manchester, UK.
Rothenberg
Marc E
ME
Lawrence
Rachel A
RA
D000818:Animals; D017178:Brugia malayi; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D047209:Eosinophil Peroxidase / Q000378:metabolism; D004802:Eosinophilia / Q000276:immunology / Q000469:parasitology; D004804:Eosinophils / Q000201:enzymology / Q000276:immunology*; D005368:Filariasis / Q000276:immunology* / Q000469:parasitology; D007113:Immunity, Innate; D015848:Interleukin-5 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008842:Microfilariae
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D015848:Interleukin-5; D047209:Eosinophil Peroxidase