Murine filariasis: interleukin 4 and interleukin 5 lead to containment of different worm developmental stages.
We compared the impact of IL-4 and IL-5 deficiency during the fully permissive infection of BALB/c mice with the rodent filaria Litomosoides sigmodontis. IL-5, in contrast to IL-4, is crucial for the containment of adult worms during short- and long-term infections. IL-5 KO mice allowed development of more larvae into adult worms and showed up to 200 times more adult worms persisting during chronic infection (day 60 until 200 post-infection). This increased persistence was accompanied by a reduction in inflammatory nodules around adult filariae. In contrast, adult worm survival and nodule formation did not differ between BALB/c wild-type mice and BALB/c IL-4 KO or BALB/c IL-4 receptor (IL-4R) alpha-chain KO mice. In both IL-4 and IL-5 KO mice microfilaraemia was greatly enhanced (160-fold) and prolonged compared to wild-type mice. This extent of susceptibility to microfilariae required the presence of adult worms in a full infection cycle since upon intraperitoneal injection of microfilariae alone they were removed from BALB/c, BALB/c IL-4 KO and BALB/c IL-4R alpha-chain KO mice with equivalent kinetics, and since microfilarial survival was only slightly increased in IL-5 KO mice (factor of 5 vs. factor of 160 in full infection). In conclusion, IL-4 and IL-5 dependent effector pathways operate against different stages of filarial worms, and IL-5 has a greater impact on parasite containment than IL-4.
Volkmann
Lars
L
Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Bain
Odile
O
Saeftel
Michael
M
Specht
Sabine
S
Fischer
Kerstin
K
Brombacher
Frank
F
Matthaei
Klaus I
KI
Hoerauf
Achim
A
D000818:Animals; D004195:Disease Models, Animal; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D005368:Filariasis / Q000188:drug therapy*; D005370:Filarioidea / Q000187:drug effects; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000172:deficiency / Q000378:metabolism; D015398:Signal Transduction
D015848:Interleukin-5; D019948:Receptors, Interleukin-4; D015847:Interleukin-4