Murine filariasis: interleukin 4 and interleukin 5 lead to containment of different worm developmental stages

Abstract

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 longterm 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) a-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 a-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.

The human parasite Loa loa in cytokine and cytokine receptor gene knock out BALB/c mice: survival, development and localization

“…These two cytokines have been previously associated with resistance of the host to infection. IL-4 and IL-5 in addition to IL-13 are required to prevent the development of adult worms as well as development of microfilaremia [17,27]. When IFN-γ in addition to IL-5 was knocked out, larvae survived only for 40 days.…”

“…The mice used in the experiment were obtained from the Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University of Bonn, Germany, where the following strains had been used and described before [17]:…”

Absence of IL-17A in Litomosoides sigmodontis-infected mice influences worm development and drives elevated filarial-specific IFN-γ

“…Protein concentrations of antigenic extracts were determined using the Advanced Protein Assay (Cytoskeleton, ORT, USA) and aliquots of sterile LsAg were frozen at − 80 °C until required. Mice were infected using infected tropical mites as previously described (Hübner et al 2009; Volkmann et al 2003) and worms were recovered from the TC of individual mice 7 and 28 days p.i. to microscopically determine life stages, gender and length.…”

NOD2 dependent neutrophil recruitment is required for early protective immune responses against infectious Litomosoides sigmodontis L3 larvae

“…Taken together with recent publications, our data support that the observed increased worm burden in NOD2 −/− is not mediated by eosinophils and mast cells. IL-5 deficient mice which lack eosinophils do not have an increased worm burden 2 and 28 days post L. sigmodontis infection42, yet IL-5 is required for vaccine induced protection and during the late phase of infection424344. Degranulation of mast cells on the other hand was previously associated with an increased vascular permeability which facilitates L. sigmodontis larval migration to the thoracic cavity45, suggesting that reduced expression of mast cell associated genes, as observed in NOD2 −/− mice, is not the driving factor for the increased worm burden in NOD2 −/− mice.…”

“…Age and sex matched mice were infected at 6–10 weeks of age with L. sigmodontis via natural infection by the intermediate host O. bacoti . Mice from both groups were exposed simultaneously to the same batch of O. bacoti mites containing infectious L. sigmodontis L3 larvae44.…”