Interleukin-4 is essential for the control of microfilariae in murine infection with the filaria Litomosoides sigmodontis - PubMed (original) (raw)

Interleukin-4 is essential for the control of microfilariae in murine infection with the filaria Litomosoides sigmodontis

L Volkmann et al. Infect Immun. 2001 May.

Abstract

Litomosoides sigmodontis is the only filaria which develops from infective larvae into microfilaria-producing adults in immunocompetent laboratory mice. In this study we report that interleukin-4 knockout (IL-4 KO) mice have an up to 100-fold-higher and a significantly prolonged microfilaremia compared to wild-type BALB/c mice, as well as 20 times more microfilariae in the thoracic cavity, the site of infection. While worm development and adult worm persistence were equivalent in IL-4 KO and wild-type mice, the fertility and length of adult female worms in IL-4 KO mice was clearly enhanced. The high susceptibility to microfilariae in IL-4 KO mice required the presence of adult worms in a full infection cycle since microfilariae loads did not differ much between IL-4 KO and wild-type mice when purified microfilariae were injected into mice. In addition, we found that eosinophilia was diminished and immunoglobulin E (IgE) was absent in IL-4 KO mice. IgE, however, does not seem to be the essential factor for microfilarial containment since microfilaremia was not elevated in B-cell KO mice. In conclusion, IL-4 is shown for the first time to be essential for the control of microfilarial loads but not of adult worm loads in a fully permissive murine filarial infection. IL-4 dependent effector pathways seem to operate on adult worms rather than directly on microfilariae.

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Figures

FIG. 1

FIG. 1

(A) Microfilaremia in infected IL-4 KO (○) or wild-type (●) mice observed over the whole time of patency. Numbers in the graph denote the range. (B) Microfilaremia in infected mice, observed in a second (and representative for a third consistent) experiment until day 77 p.i. (C) MF levels in the thoracic cavity at day 77 p.i. The number of MF is up to 200-fold higher in IL-4 KO mice (white bar) compared to the wild-type mice (black bar). Significant differences are denoted by asterisks as follows: ∗, P < 0.05; ∗∗, P < 0.03; ∗∗∗, P < 0.01 (Mann-Whitney U test).

FIG. 1

FIG. 1

(A) Microfilaremia in infected IL-4 KO (○) or wild-type (●) mice observed over the whole time of patency. Numbers in the graph denote the range. (B) Microfilaremia in infected mice, observed in a second (and representative for a third consistent) experiment until day 77 p.i. (C) MF levels in the thoracic cavity at day 77 p.i. The number of MF is up to 200-fold higher in IL-4 KO mice (white bar) compared to the wild-type mice (black bar). Significant differences are denoted by asterisks as follows: ∗, P < 0.05; ∗∗, P < 0.03; ∗∗∗, P < 0.01 (Mann-Whitney U test).

FIG. 1

FIG. 1

(A) Microfilaremia in infected IL-4 KO (○) or wild-type (●) mice observed over the whole time of patency. Numbers in the graph denote the range. (B) Microfilaremia in infected mice, observed in a second (and representative for a third consistent) experiment until day 77 p.i. (C) MF levels in the thoracic cavity at day 77 p.i. The number of MF is up to 200-fold higher in IL-4 KO mice (white bar) compared to the wild-type mice (black bar). Significant differences are denoted by asterisks as follows: ∗, P < 0.05; ∗∗, P < 0.03; ∗∗∗, P < 0.01 (Mann-Whitney U test).

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