Absence of regulatory IL-10 enhances innate protection against filarial parasites by a neutrophil-independent mechanism.
Brugia malayi causes the major tropical disease, lymphatic filariasis. Chronicity of disease is associated with generation of regulatory cells secreting IL-10 and/or TGF-beta. Previous work has shown that the rate of microfilariae (Mf) clearance from the blood is mouse strain-dependent. Here, we show that IL-10 plays an important role in preventing the clearance of Mf. Indeed, anti-IL-10 antibody treatment increases the rate of Mf clearance from the bloodstream in both rapid-Mf-clearing CBA/Ca and slow-clearing C57Bl/6 mice. In addition, IL-10(-/-) mice implanted intraperitoneally with Mf-producing adult nematodes have significantly lower Mf, but not adults, in comparison with wild-type mice at 3 weeks post-implantation (p.i.). Clearance of Mf from the peritoneal cavity of IL-10(-/-) mice is associated with a dramatic infiltration of neutrophils. Furthermore, rapid-Mf-clearing CBA/Ca mice have a dramatic blood neutrophilia at 24 h p.i., whereas slow-clearing C57Bl/6 mice show no such neutrophilia. Thus, neutrophils may play a role as effector cells in microfilarial infection. We therefore treated mice with anti-granulocyte antibody to abolish neutrophil recruitment during Mf infection i.v. Although anti-granulocyte treatment severely depleted neutrophils, it did not significantly reduce the rate of B. malayi Mf clearance either during primary infection or during a challenge following antigen sensitization.
Simons
J E
JE
School of Biological Sciences, University of Manchester, Manchester, UK.
Gray
C A
CA
Lawrence
R A
RA
D000818:Animals; D017178:Brugia malayi / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D005260:Female; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D010529:Peritoneal Cavity / Q000469:parasitology
D016753:Interleukin-10