<i>Schistosoma mansoni</i> Tegument (Smteg) Induces IL-10 and Modulates Experimental Airway Inflammation

<div><p>Background</p><p>Previous studies have demonstrated that <i>S</i>. <i>mansoni</i> infection and inoculation of the parasite eggs and antigens are able to modulate airways inflammation induced by OVA in mice. This modulation was associated to an enhanced production of interleukin-10 and to an increased number of regulatory T cells. The <i>S</i>. <i>mansoni</i> schistosomulum is the first stage to come into contact with the host immune system and its tegument represents the host-parasite interface. The schistosomula tegument (Smteg) has never been studied in the context of modulation of inflammatory disorders, although immune evasion mechanisms take place in this phase of infection to guarantee the persistence of the parasite in the host.</p><p>Methodology and Principal Findings</p><p>The aim of this study was to evaluate the Smteg ability to modulate inflammation in an experimental airway inflammation model induced by OVA and to characterize the immune factors involved in this modulation. To achieve the objective, BALB/c mice were sensitized with ovalbumin (OVA) and then challenged with OVA aerosol after Smteg intraperitoneal inoculation. Protein extravasation and inflammatory cells were assessed in bronchoalveolar lavage and IgE levels were measured in serum. Additionally, lungs were excised for histopathological analyses, cytokine measurement and characterization of the cell populations. Inoculation with Smteg led to a reduction in the protein levels in bronchoalveolar lavage (BAL) and eosinophils in both BAL and lung tissue. In the lung tissue there was a reduction in inflammatory cells and collagen deposition as well as in IL-5, IL-13, IL-25 and CCL11 levels. Additionally, a decrease in specific anti-OVA IgE levels was observed. The reduction observed in these inflammatory parameters was associated with increased levels of IL-10 in lung tissues. Furthermore, Smteg/asthma mice showed high percentage of CD11b⁺F4/80⁺IL-10⁺ and CD11c⁺CD11b⁺IL-10⁺ cells in lungs.</p><p>Conclusion</p><p>Taken together, these findings demonstrate that <i>S</i>. <i>mansoni</i> schistosomula tegument can modulates experimental airway inflammation.</p></div

Smteg treatment reduced inflammatory parameters of airway inflammation.

<p>The production of (<b>A</b>) IL-5, (<b>B</b>) IL-13, (<b>C</b>) CCL11 and (<b>D</b>) IL-10 was evaluated in the lungs of mice. The Smteg/Asthma group presented lower levels of inflammatory cytokines (A-C) while showed up-regulation of IL-10 (D), compared to Asthma group. Moreover, (<b>E</b>) OVA-specific IgE levels in sera of mice were reduced due to Smteg treatment. *<i>p</i> < 0,05; Student's t test; O.D = Optical Density. Data are representative of 2 independent experiments. Results are presented as mean ± SD.</p

Induction of airway inflammation and inoculation of Smteg in murine model.

<p>(<b>A</b>) BALB/c mice were sensitized with OVA on days 0 and 14 and received Smteg on day 7. Mice were challenged with aerosol from days 21 to 25 and euthanized on day 26. (<b>B</b>) Mice received Smteg or PBS and were sacrificed after 14 days. s.c.–subcutaneous, i.p.–intraperitoneal, BAL- bronchoalveolar lavage.</p

Lungs histopathology analysis.

<p>Upper panel shows lungs stained with HE and bottom panel shows lungs stained with Gomori Trichrome. Lungs from PBS control group (<b>A</b> and <b>D</b>) presented almost no infiltrate and collagen deposition. Asthmatic mice (<b>B</b> and <b>E</b>) presented intense inflammatory infiltrate and collagen deposit. Animals treated with Smteg (<b>C</b> and <b>F</b>) showed reduced levels of these parameters. Blue arrows point to peribronchiolar area and red arrows point to perivascullar area. Magnification 10x; bars 100μm. Semiquantitative analysis of inflammation (<b>G</b>) was performed in lung sections from five animals per group in magnification of 20x. Increased inflammation was observed in Asthma group compared to PBS and Smteg treated mice. Eosinophil number was determined in lung section (<b>H</b>) from five animals per group at a magnification of 63x. Results were expressed as the mean number of eosinophil/100mm² +/- SD. Smteg treatment significantly decreased the number of eosinophils in the lung. Collagen deposition was measured by morphometric analysis of lung sections stained with Gomori Trichrome (I) at a magnification of 10x. Results are expressed as area of fibrosis (μm²)/mm² of lung tissue. Significant reduction in collagen deposition was observed in Smteg treated group. Significant differences between groups are pointed in the Graphics. Data are representative of 2 independent experiments.</p

Increased production of IL-10 by monocytes in lungs of Smteg treated mice.

<p>Lungs cells were stained as described in Materials and Methods. Analysis strategy was represented in <b>A</b>. Mice of the Smteg/Asthma group presented higher percentage of IL-10 producing cells expressing (<b>B</b>) macrophage or (<b>C</b>) dendritic cells markers compared to Asthma group. *<i>p</i> < 0,05; Student's t test.</p