IL-5 is essential for vaccine-induced protection and for resolution of primary infection in murine filariasis.
The pathways conferring immunity to human filariases are not well known, in part because human-pathogenic filariae do not complete a full life cycle in laboratory mice. We have used the only fully permissive infection of mice with filariae, i.e., infection of BALB/c mice with the rodent filarial nematode Litomosoides sigmodontis. Our previous results showed that worm development is inversely correlated with Th2 cytokine production and eosinophilia. The scope of the present study was to directly elucidate the role of interleukin-5 (IL-5) and eosinophils in controlling the development of L. sigmodonitis after vaccination and in primary infection. BALB/c mice immunized with irradiated third-stage larvae (L3) were confirmed to have elevated IL-5 levels as well as high subcutaneous eosinophilia and to attack and reduce incoming larvae within the first 2 days, resulting in 70% reduction of worm load. Treatment of vaccinated mice with anti-IL-5 antibody (TRFK-5) suppressed both blood and tissue eosinophilia and completely abolished protection. This demonstrates, for the first time in a fully permissive filarial infection, that IL-5 is essential for protection induced by irradiated L3 larvae. In contrast, in primary-infected mice, anti-IL-5 treatment did not modify filarial infection within the 1st month, most likely because during primary infection IL-5-dependent mechanisms such as subcutaneous eosinophilia are induced too late to disturb worm establishment. However, there is a role for IL-5 late in primary infection where neutrophil-dependent worm encapsulation is also under the control of IL-5.
Martin
C
C
Institut de Systématique CNRS FR 1541, Biologie Parasitaire, Muséum National d'Histoire Naturelle, Paris, France.
Al-Qaoud
K M
KM
Ungeheuer
M N
MN
Paehle
K
K
Vuong
P N
PN
Bain
O
O
Fleischer
B
B
Hoerauf
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D005368:Filariasis / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D005370:Filarioidea / Q000254:growth & development / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology*; D007378:Interleukins / Q000096:biosynthesis; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination; D014612:Vaccines / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015848:Interleukin-5; D007378:Interleukins; D014612:Vaccines