Schistosoma japonicum infection downregulates house dust mite-induced allergic airway inflammation in mice - PubMed (original) (raw)

Schistosoma japonicum infection downregulates house dust mite-induced allergic airway inflammation in mice

Sugan Qiu et al. PLoS One. 2017.

Erratum in

Abstract

The "hygiene hypothesis" is a theory try to explain the dramatic increases in the prevalence of autoimmune and allergic diseases over the past two to three decades in developed countries. According to this theory, reduced exposure to parasites and microorganisms in childhood is the main cause for the increased incidences of both T helper 1 (Th1)-mediated autoimmunity and Th2-mediated allergy. In this study, we investigated the impact of Schistosoma japonicum infection on the allergic airway inflammation induced by repeated intracheal inoculations of house dust mites (HDM), which is a Th17 and neutrophils dominant murine asthma model, mimicking severe asthma. We found that S. japonicum infection downregulated airway hyperresponsiveness. The infiltrating cells, Th17 and Th2 effector cytokines in the bronchoalveolar lavage (BAL) fluids and lungs were significantly reduced in the infected mice. Our findings indicated that S. japonicum infection was able to effectively inhibit host's allergic airway inflammation, which may be related to the upregulated Treg cells upon infection. To our knowledge, it is the first study to reveal the impact of S. japonicum infection on house dust mite induced severe asthma. More in depth investigation is need to elucidate the underlying mechanisms.

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Conflict of interest statement

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

Figures

Fig 1

Fig 1. S. japonicum infection inhibits HDM-induced airway inflammation at early phase.

(A) To induce allergic airway inflammation, both infected and uninfected C57BL/6 mice were inoculated intratracheally (i.t.) with HDM. In the early immunization regimen, HDM inoculations started at 3 wks post the infection with S. japonicum (S.j.). Control groups were inoculated i.t. with PBS alone. Mice were sacrificed 24 h after the last challenge. (B) The total cells in BAL fluids were counted by using a hemacytometer. (C) Differential cell counts of >400 cells were performed on cytospins stained with Kwik-Diff. The numbers of eosinophils (Eo), macrophages (Mϕ), neutrophils (Neu), and lymphocytes (Lym) in BAL are shown. (D-E) Representative Kwik-Diff staining of BAL cells and H&E staining of lung tissue sections. (F) Cytokine levels in BAL fluids were determined by ELISA. (G) Total RNA from the right lower lobe of the lungs was extracted for real-time PCR analysis for IL-4, eotaxin, IFN-γ and Gob-5. Data are normalized to an 18S reference and expressed as arbitrary units. Results are expressed as mean+SE (B-C, F-G), representative of two independent experiments (n = 5–10 per group). Compared to uninfected and HDM immunized mice, *p<0.05; **p<0.01.

Fig 2

Fig 2. S. japonicum infection inhibits HDM-induced airway inflammation at late phase.

(A) In the late immunization regimen, HDM inoculations started at 5 wks post infection. The experiments were performed similarly as Fig 1. Total and differential cell counts of BAL cells (B-C), representative Kwik-Diff staining for BAL cytospins and H&E staining of lung tissue sections (D-E), cytokine levels in BAL fluids (F), and mRNA levels in the lungs (G) are shown. Results are representative of two independent experiments (n = 5–9 per group). Compared to uninfected and HDM immunized mice, *p<0.05; **p<0.01.

Fig 3

Fig 3. Serum OVA-specific IgE is reduced in S. japonicum infected mice.

In the same experiments as Fig 2, serum levels of OVA-specific IgE, IgM, IgG and IgG subclasses were assayed by ELISA (mean+SE). **p<0.01 compared to uninfected and HDM immunized mice.

Fig 4

Fig 4. Cytokine dynamics in vivo post infection.

C57BL/6 mice were infected with S. japonicum. The levels of IFN-γ, IL-4, IL-10, and IL-17 cytokines in the peripheral blood were assayed at indicated times by IVCCA. Results are representative of two independent experiments (n = 5–9 per group). Compared to uninfected mice, **p<0.01.

Fig 5

Fig 5. Treg cells expand after S. japonicum infection.

Treg cells in the spleens were determined by Flow cytometry gated on CD4+ cells. Percentages of Treg cells (CD4+CD25+Foxp3+) cells are shown in representative dot plots (A), and summarized in a graph (B). Results are representative of two independent experiments (n = 5–6 per group).

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