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. 1999 Aug;67(8):4183-90.
doi: 10.1128/IAI.67.8.4183-4190.1999.

Infection of mice lacking interleukin-7 (IL-7) reveals an unexpected role for IL-7 in the development of the parasite Schistosoma mansoni

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Infection of mice lacking interleukin-7 (IL-7) reveals an unexpected role for IL-7 in the development of the parasite Schistosoma mansoni

I Wolowczuk et al. Infect Immun. 1999 Aug.

Abstract

A single intradermal administration of recombinant interleukin-7 (IL-7) has been shown to aggravate the course of murine schistosomiasis, to favor the development of Th2-associated antibodies specific for the parasite, and to alter migration kinetics and/or migratory route of the parasite within its vertebrate host. Here we show that after infection of IL-7-deficient mice with Schistosoma mansoni, the predominant parasite-specific humoral response follows a Th1 pattern, and the development of the parasite is greatly impaired. In IL-7-deficient mice, increased numbers of larvae reach the lungs and fewer larvae reach the liver, compared to control mice. In the absence of IL-7, female worms show an altered fecundity, leading to decreased numbers of eggs trapped in the tissues and to an amelioration of the pathology of the infected host. The most striking observation is the blockade of parasite growth in an IL-7-defective environment, leading to dwarf male and female worms. The results of this study have important implications for the role of IL-7 in the host-parasite relationship and show how parasites can disable or evade the host immune response.

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Figures

FIG. 1
FIG. 1
Total adult worm burden (A), numbers of eggs expressed per gram of liver (B), and numbers of eggs expressed per gram of liver and per female worm (C) in IL-7+/+ and IL-7−/− S. mansoni-infected animals. Each datum point shows the value for one mouse (six mice per group), and the horizontal bar shows the mean for that group of mice. This experiment is representative of four independent experiments. Statistical analysis using the Student’s t test gave P values of 0.15 (A), 0.002 (B), and 0.05 (C).
FIG. 2
FIG. 2
Morphology of worms (males and females) collected from IL-7+/+ infected animals (+/+) and IL-7−/− infected animals (−/−) at day 42 (A) and day 80 (B) following infection with S. mansoni cercariae.
FIG. 3
FIG. 3
Percentages of dead eggs (A) (P = 0.005) and mature eggs (B) (P = 0.014) laid by females in the livers of IL-7+/+ and IL-7−/− animals. Each datum point shows the value for one mouse, and the horizontal bar shows the mean for that group.
FIG. 4
FIG. 4
Pathology of livers of IL-7+/+ and IL-7−/− animals infected with S. mansoni for 80 days. (A) Collagen measurement (in micrograms per milligram of protein). Results are expressed for each individual mouse and are representative of three independent experiments. The horizontal bars show the means for the two groups of mice which were significantly different (P = 0.001). (B) Histological staining for collagen on liver sections of IL-7+/+ and IL-7−/− infected mice 80 days p.i. Syrius red F3B stained collagen in red. Magnification, ×ばつ100.
FIG. 4
FIG. 4
Pathology of livers of IL-7+/+ and IL-7−/− animals infected with S. mansoni for 80 days. (A) Collagen measurement (in micrograms per milligram of protein). Results are expressed for each individual mouse and are representative of three independent experiments. The horizontal bars show the means for the two groups of mice which were significantly different (P = 0.001). (B) Histological staining for collagen on liver sections of IL-7+/+ and IL-7−/− infected mice 80 days p.i. Syrius red F3B stained collagen in red. Magnification, ×ばつ100.
FIG. 5
FIG. 5
Migration of S. mansoni schistosomula to the lungs in IL-7+/+ and IL-7−/− S. mansoni-infected mice day 6 p.i. Each datum point shows the value for one mouse. The horizontal bars show the mean values for the two experimental groups which were significantly different (P = 0.0035). This experiment was performed twice and gave similar results.
FIG. 6
FIG. 6
Specific antibody response in IL-7+/+ and IL-7−/− mice during the course of S. mansoni infection. Total IgG, IgG1, and IgG2a specific for SWAP (A) egg-specific IgG, IgG1, and IgG2a (SEA) (B) are shown. In this experiment, seven animals per group were infected and repeatedly bled on days 0, 28, 35 and 42 following infection. For each time point, sera from the 7 animals were pooled and tested by specific ELISA. Each test was done in triplicate. The y-axis label (optical density at 492 nm [O.D. (492 nm)] and symbol key shown in the top bar graph in panel A apply to all bar graphs in the figure.

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