Development of adult worms and granulomatous pathology are collectively regulated by T- and B-cells in mice infected with Schistosoma japonicum - PubMed (original) (raw)

Development of adult worms and granulomatous pathology are collectively regulated by T- and B-cells in mice infected with Schistosoma japonicum

Hongbin Tang et al. PLoS One. 2013.

Erratum in

Abstract

Schistosoma blood flukes, which cause schistosomiasis affecting 200 million people in the world, are dependent on signals from host CD4(+) T cells to facilitate parasite growth and development in the mammalian host and to induce Th2-biased inflammatory granulomas. B cells, however, are reported to down-regulate granulomatous pathology in schistosomiasis, but not to affect the development of blood flukes together with CD4(+) T lymphocytes. Thus it is not clear whether B cells mediate parasite development, reproduction and egg granuloma formation of schistosomes without the help of CD4(+) T lymphocytes. Using mice that have severe combined immunodeficiency (scid) and mice lacking T cells (nude), we found that the absence of B cells can more seriously hamper the development and paring of adult worms, but granuloma formation of Schistosoma japonicum in scid mice was not down-regulated comparing with that in nude mice. The level of IL-10 in the sera of nude mice was significantly higher than of scid mice at 43 days post infection (p.i.). Thus multiple mechanisms of immune modulation seem to be involved in parasite development and reproduction by helminth-induced regulatory B cells. Our findings have significance for understanding the molecular connections between schistosomes and T- and B-cells, indicating that more research is needed to develop efficient vaccine-based therapies for schistosomiasis.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. The effects of CD4+ T cell deficiency on the development of worms.

(A) Flow cytometric analysis of peripheral blood CD4+ lymphocytes in scid, nude and BALB/c mice, recovered at 43 days p.i. Presented are % of cells detected in CD3 gate as a mean from one of 2 experiments with 4 mice per group. (B) Parasites were recovered from the portal tract at 29, 36, 43 days p.i., and male and female worm sizes were determined based on digital micrographs. Mean values are represented by horizontal bars. (C) Total number of worms and worm pairs in nude and BALB/c mice at 29, 36, 43 days p.i… Data are represented as median± SEM.

Figure 2

Figure 2. B cells and T cells play crucial roles for development and reproduction of schistosomes.

(A) Flow cytometric analysis of peripheral blood B lymphocytes in scid, nude and BALB/c mice; peripheral blood was recovered at 43 days p.i… Presented are, % of cells in the CD45R gate as mean from one of two experiments), with 4 mice per group. (B) Sizes of parasites from scid and nude mice were measured from digital micrographs. (C) Total number of worms and worm pairs recovered from scid, nude, or BALB/c mice were compared at 29, 36, 43 days p.i… Data are represented as median± SEM. (D) Egg production by schistosome pairs, as in C. (E) IL-10 cytokine secretions, measured by ELISA, in scid (white bars), nude (gray bar) and BALB/c (black bar) mice at 29, 36, 43 days p.i. (F) Representative micrographs of parasites recovered from BALB/c mice, nude mice, or scid mice at the time points indicated p.i. (10× magnification).

Figure 3

Figure 3. Hepatic granuloma size and fibrosis is reduced in nude mice versus BALB/c mice, but the same as scid mice.

(A) granuloma sizes calculated from isolated granulomas at 43 days after infection calculated from three separate granulomas per individual animal. (B) a typical well-formed and multi-cellular granuloma with minimal hepatocyte necrosis (×200) includes a large number of eosinophils in BALB/c. granuloma with a much reduced cellular infiltration and obvious hepatocyte necrosis surrounding egg show the relative selective depletion of eosinophils and cellularity in nude and scid, but there is no difference significant between the two.

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