|Year : 2015 | Volume
| Issue : 3 | Page : 642-649
Schistosoma mansoni infection or soluble egg antigen immunization can reduce allergic airway diseases
Nashaat E Nassef, Wafaa M El-Kersh, Nadia S El-Nahas, Salwa A Shams El-Din, Shaimaa A Sharaf El-Deen
Department of Parasitology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||15-Apr-2014|
|Date of Acceptance||05-May-2014|
|Date of Web Publication||22-Oct-2015|
Salwa A Shams El-Din
Department of Parasitology, Faculty of Medicine, 32511 Shibin El-Kom-YassinAbd El-Ghaffar Street
Source of Support: None, Conflict of Interest: None
The aim of the study was to investigate the impact of Schistosoma mansoni infection and soluble egg antigen (SEA) immunization on allergic airway diseases and to study the involved immune-modulation mechanisms.
Schistosomiasis and allergic airway diseases are common health problems that affect a wide range of population. Many studies showed that there is an inverse relationship between prevalence of Schistosoma and allergic airway diseases.
Materials and methods
The mice groups were either infected with S. mansoni or SEA immunized or noninfected. Airway allergy was induced in laboratory mice by ovalbumin. Thereafter, the degree of lung inflammation was determined by histopathology. Immune response was studied by immune-histochemical examination of regulatory T (T-reg), CD4+ and CD8+ cells, and serum antiovalbumin IgE level was determined by ELISA.
The infected and immunized groups showed significant reduction in lung pathology, CD4+ cell infiltration of lungs and serum antiovalbumin IgE level than the control group. This was associated with a significant increase in the immune-suppressor T-reg cells and CD8+ cells infiltration of lungs.
S. mansoni infection or SEA immunization have downregulating effects on ovalbumin-induced experimental allergic airway diseases. These effects could be attributed to increased activation of T-reg cells and CD8+ cells, which downregulate the immune response.
Keywords: Immune response, immunization, ovalbumin, Schistosoma mansoni, soluble egg antigen, T-reg cells
|How to cite this article:|
Nassef NE, El-Kersh WM, El-Nahas NS, Shams El-Din SA, Sharaf El-Deen SA. Schistosoma mansoni infection or soluble egg antigen immunization can reduce allergic airway diseases. Menoufia Med J 2015;28:642-9
|How to cite this URL:|
Nassef NE, El-Kersh WM, El-Nahas NS, Shams El-Din SA, Sharaf El-Deen SA. Schistosoma mansoni infection or soluble egg antigen immunization can reduce allergic airway diseases. Menoufia Med J [serial online] 2015 [cited 2020 Apr 3];28:642-9. Available from: http://www.mmj.eg.net/text.asp?2015/28/3/642/167782
| Introduction|| |
Schistosomiasis is the third most frequent parasitic disease affecting mankind. It ranks immediately after malaria and amoebiasis . Many control programs were directed against Schistosoma and led to a general decline in its prevalence. For example, Egyptian prevalence has declined from over 50% by the year 1983 to 12% by the year 2005 ,.
Allergic airway diseases are also common. They occur because of an exaggerated immune response (hypersensitivity) to different antigens leading to activation of different cells responsible for immune response, mainly Th2 cells. Immune response to airway allergen begins with recognition by its specific IgE bound to mast cells and basophils. This recognition is followed by early-phase and late-phase responses, which lead to secretion of many cytokines that activate many immune cells ,.
In contrast to Schistosoma, the prevalence of allergic airway diseases has increased over the past decades, especially in developed areas. It was noticed that this increased prevalence was associated with a general decline in bacterial and parasitic infections in these areas ,. This was reported in many epidemiological and clinical studies, which showed an inverse correlation between allergic airway diseases and infections. These findings lead to development of 'hygiene hypothesis', which suggested that exposure to certain infections may have an inhibitory effect on the development of allergy and asthma ,,.
Some experimental studies showed a protective effect of some chronic helminth infections including Schistosoma mansoni on the development of allergic airway inflammation ,.
The influence of parasitic infections on the development of allergy has been less well studied. Some epidemiological and clinical studies have suggested that chronic helminth infections may inhibit allergy, although it is also controlled by Th2 response ,. Although allergy and helminth infections are controlled by Th2 responses, they are functionally different. Allergic Th2 response is an abnormality in human, whereas Th2 responses to helminth infections are important protective mechanism against these parasitic infections. Many immune-modulatory effects of helminth infection also have been identified during immune reaction of the host against them .
Acute schistosomiasis is mainly controlled by Th1 response and its related cytokines ,. However, Th2 response increases as the infection moves toward chronicity, especially after onset of egg deposition . This Th2 response is regulated by many cells and cytokines, mainly regulatory T (T-reg) cells and its cytokines interleukin (IL)-10 and transforming growth factor (TGF)-b . T-reg cells were found to be deficient in asthmatic patients, and it was also reported that many antiasthmatic drugs increase T-reg cells as a part of their action .
The aim of the present work was to study the effect of experimental S. mansoni infection on induced allergic airway diseases. The study also aimed to study the effect of immunization by S. mansoni soluble egg antigen (SEA) on the same disease through histopathological detection of cellular immune response of T-reg, CD4+ and CD8+ cells and through estimation of humoral immune response by serum antiovalbumin IgE level.
| Materials and methods|| |
Sixty BALB/c mice (6-8-week-old) were obtained from the Schistosome Biological Supply Program, Theodor Bilharz Research Institute (Giza, Egypt) and kept under standard housing conditions in their animal house. All procedures met the International Guiding Principles for Biomedical Research Involving Animals as issued by the International Organizations of Medical Sciences (http://www.cioms.ch/).
Mice were divided into six groups. Each group consisted of 10 mice. Group I (GI) was sensitized by ovalbumin. Group II (GII) was infected with S. mansoni then sensitized by ovalbumin after onset of egg deposition as detected by stool examination. Group III (GIII) received SEA immunization then sensitized by ovalbumin after the fourth dose of SEA. Group IV (GIV) was infected with S. mansoni cercariae only. Group V (GV) was immunized by SEA, whereas group VI (GVI) was the nonovalbumin sensitized nonimmunized non-S. mansoni-infected group (the negative control group).
Infection of mice with Schistosoma mansoni 
Mice (GII and GIV) were infected with 50-100 S. mansoni cercariae (Egyptian strain) by subcutaneous injection. Stool examination from the day 45 postinfection was performed to ensure completion of the cycle and onset of the chronic stage by presence of S. mansoni eggs in stool of mice.
Immunization by Schistosoma mansoni soluble egg antigen
S. mansoni SEA was purchased from Schistosome Biological Supply Program, Theodor Bilharz Research Institute. The crude SEA preparation was purified, sterilized by filtration through 0.45-μm filters (Nalgene Brand Product; Sybran Corp., Rochester, New York, USA) and the protein content was estimated using the Bio-Rad Kit (Bio-Rad Laboratories, Hercules, California, USA) . The immunized groups (GIII and GV) were intraperitoneally injected with four doses (10 μg of the SEA each in 10 μl PBS) given with 2 days separation between each dose .
Sensitization of mice by ovalbumin allergen 
To induce allergic airway inflammation, mice (GI, GII and GIII) were sensitized with ovalbumin (Worthington Biochemical Cooperation, Lakewood, New Jersey, USA) using 20 μg of ovalbumin in 2 mg of aluminium hydroxide gel adjuvant in a total volume of 200 μl by intraperitoneal injection (days 60 and 75). On days 88-89, they were challenged with intranasal ovalbumin (50 μg ovalbumin in 50 μl PBS). Negative control animals were injected with aluminium hydroxide in PBS intraperitoneally and intranasally challenged with PBS instead of ovalbumin. S. mansoni infection (GII and GIV) and SEA immunization (GIII and GV) were totally completed before ovalbumin sensitization. All mice were killed on the day 90 of the experiment.
Histopathological examination of lung tissue 
Lung tissue of mice from all groups was preserved in formalin 10% and stained with haematoxylin and eosin. Stained slides were microscopically examined to determine the degree of lung inflammation as free, mild, moderate or severe. The degree of inflammation was categorized into four levels: free (no inflammation), mild (1-2 foci of inflammation/section), moderate (3-6 foci of inflammation/section) and severe (> 6 foci of inflammation/section). Three slides were evaluated for each mouse. The mean of all the individual scores was calculated and used for analysis .
Immunohistochemistry for Foxp3+ T-reg cells, CD4+ cells and CD8+ cells 
Lung tissue sections of 4-μm thickness were deparaffinized, rehydrated and then incubated with rabbit monoclonal antimouse Foxp3+ monoclonal antibodies (Aviva Systems Biology, San Diego, California, USA), rabbit monoclonal antimouse antibodies against CD4+ cells (Abcam, Cambridge, Massachusetts, USA), or rabbit monoclonal antimouse antibodies against CD8+ cells (Abcam). This step was followed by incubation with biotinylated goat antipolyvalent secondary antibody. Enzyme conjugate streptavidin peroxidase was applied before enzyme substrate chromogen solution. Counter staining was performed using Mayers hematoxylin. Positivity was considered when any cell showed brown membranous or membranocytoplasmic staining. Stained cells of lung tissues were counted from 10 randomly chosen high power field (h.p.f.).
Estimation of antiovalbumin IgE levels 
The levels of antiovalbumin IgE in serum were estimated by ELISA (Mouse Serum Antiovalbumin IgE Antibody Assay Kit; Chondrex Inc., Redmond, Washington, USA). The assays were performed according to the manufacturer's protocol.
The collected data were tabulated and analyzed by SPSS statistical package (version 13; SPSS Inc., Chicago, Illinois, USA). The Kruskal-Wallis test for nonparametric data was used. P-values of less than 0.05 were considered statistically significant.
| Results|| |
Data in [Table 1] and [Figure 1] show that both S. mansoni infection and SEA immunization decreased incidence of severe lung inflammation, which was of the most prevalent degree in GI. Severe inflammation was totally absent in GII and only 20% in GIII. Free lungs prevailed in GIV, whereas GV and GVI were totally free of inflammation.
|Figure 1: Lung tissue of ovalbumin sensitized group (group I) showing severe lung congestion (C) associated with dense chronic infl ammatory infiltrate (I) of lung tissue (haematoxylin and eosin, ×200).|
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|Table 1: Comparison of the degree of lung inflammation between the studied groups|
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[Table 2] describes T-reg cells count/10 h.p.f. in the studied groups. Both GII and GIII had significantly higher counts than GI. The difference between GII and GIII was insignificant (P > 0.05) [Figure 2] and [Figure 4].
|Figure 2: Lung tissue of Schistosoma mansoni-infected ovalbumin sensitized group (group II) showing moderate chronic inflammatory infiltrate (I) in peribronchial and interstitial tissue together with tissue congestion (C) (haematoxylin and eosin, ×200).|
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|Table 2: Comparison between mean T regulatory cell count/10 high power field among studied groups|
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CD4+ cells count/10 h.p.f. described in [Table 3] shows that lung tissue of both GII and GIII showed significant reduction in CD4+ cells infiltration than GI, which was the most infiltrated by CD4+ cells [Figure 3] and [Figure 5], whereas the difference between GII and GIII was insignificant (P > 0.05).
Data in [Table 4] show that CD8+ cells count/10 h.p.f. in both GII and GIII was significantly higher than GI. The difference between GII and GIII was insignificant (P > 0.05).
|Figure 3: Lung tissue of soluble egg antigen immunized ovalbumin sensitized group (group III) showing congested lung tissue (C) together with mild peribronchial and interstitial chronic lymphoplasmacytic inflammation (I) (haematoxylin and eosin, ×200) .|
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|Figure 4: Membranous expression of Foxp3 in some cells (red arrows) in lung tissue of ovalbumin sensitized group (group I) (immune-stain reaction for Foxp3, ×400) .|
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|Figure 5: Lung tissue of ovalbumin sensitized group (group I) showing strong membranous CD4 expression in many cells (red arrows) in the interalveolar septae (immune-stain reaction for CD4, ×400 ).|
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|Table 3: Comparison between mean T helper (CD4+) cell count/10 high power fi eld among studied groups|
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|Table 4: Comparison between mean T cytotoxic (CD8+) cell count/10 high power fi eld among studied groups|
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[Table 5] shows that the mean CD4+/CD8+ cell ratio in both GII and GIII was significantly lower than GI. Both GII and GIII were insignificantly different (P > 0.05).
|Table 5: Comparison between the mean CD4+/CD8+ cell ratio among studied groups|
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[Table 6] describes the mean value of serum antiovalbumin IgE. Both GII and GIII had significantly lower value than GI. Insignificant difference was found between GII and GIII (P > 0.05).
|Table 6: Comparison between mean serum antiovalbumin IgE level among studied groups|
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| Discussion|| |
There is an evidence that decreased helminthic infections in different countries is associated with increased incidence of allergic diseases ,. The present study investigated whether S. mansoni infection could affect the pathogenesis of ovalbumin-induced allergic airway diseases and whether SEA immunization has the same effects as infection.
In the present study, the results showed that the infected group (GII) had significant reduction in the incidence of severe lung inflammation than the pure ovalbumin group (GI). This suggests immune-downregulating effect of S. mansoni infection on the immunological pathway of allergic airway diseases, which is more or less similar in infection and SEA immunization. This reduction in inflammation correlates with significant increase in T-reg cells in the infected and immunized groups, which are known as important immune-suppressor cells. They express the immune-suppressive cytokine TGF-b, which blocks IL-2 production by T helper cells. Blocking of IL-2 prevents differentiation and proliferation of T cells, natural killer cells, and other immune system cells ,. It increases activation of T-reg cells themselves and expression of Foxp3 protein, which controls the development and functions of T-reg cells. The T-reg cells act also in a cytokine-independent manner through cell contact-dependent mechanisms .
Similar results were recorded in a study on Schistosoma japonicum in which lung inflammation was decreased in ovalbumin-induced bronchial asthma in the infected mice groups. These results were attributed to activation of T-reg cells by infection or the transferred dendritic cells .
Treatment of S. mansoni infection or depletion of T-reg cells lead also to aggravation of asthmatic symptoms in murine ovalbumin-induced bronchial asthma. This supported the important role of T-reg cells in downregulation of the asthmatic pathway .
In contrast, a recent study  reported potent lung inflammation following intravenous injection of S. mansoni eggs in experimental mice. This inflammation was found to be caused by egg emboli that were carried to the lungs through the pulmonary vessels and trapped in the lung parenchyma.
In the present study lung T-reg cells showed significant increase in the infected and immunized asthmatic groups (GII and GIII) than the pure ovalbumin group (GI). This significant increase can explain the significant suppression of the immune response to ovalbumin allergen in both infected and immunized groups. T-reg cells are normally activated in S. mansoni infection as a part of the immune response that limits the damage and excessive fibrosis, which can occur with exaggerated Th2 response . The nonsignificant difference detected between GII and GIII clarifies similar effects of both whole infection and SEA immunization on T-reg cells stimulation.
Similarly, S. japonicum infection was reported to have an upregulating effect on T-reg cells. Authors related this increase to immune evasion of S. japonicum. They proved their view by the decrease in worm load in T-reg cells-depleted mice .
The immune suppressive role of T-reg cells on bronchial asthma was also reported by Choi et al. , who proved that bee venom treatment suppressed the production of IL-2, IL-4, and IL-17 and augmented the production of IL-10 by T-reg cells.
The present study showed significant reduction in CD4+ lymphocytes infiltrating the lung in both GII and GIII. These results can be due to the downregulating effects of both S. mansoni infection and SEA immunization. These results are confirmed by the fact that CD4+ lymphocytes play an important role in allergic immune response especially the late phase, and their reduction denotes lesser inflammation .
Similarly, another study reported that proportion of CD4+ T helper cells with respect to T-reg cells in the spleens and mesenteric lymph nodes decreases gradually as the S. japonicum infection becomes more chronic. This was explained by the suppressive role of T-reg cells .
S. mansoni infection and SEA immunization also had upregulating effects on CD8 + cells, which was significantly increased in both groups (GII and GIII) than the pure ovalbumin group (GI). These findings could be attributed to increased T-reg cells in the infected or immunized groups, which produce TGF-b that stimulates proliferation and immune-suppressive functions of CD8+ cells .
Similarly, Du et al.  reported that the mice groups infected with S. japonicum or immunized with SEA showed significantly higher percentage of CD8+ cells.
Mulu et al.  also reported increased CD8+ cells in the peripheral blood of intestinal helminthes-infected AIDS patients (Ascaris lumbricoides, hook worms, Strongyloides stercoralis, Trichuris trichiura, and S. mansoni) than nonhelminth-infected ones.
In the present work, comparison of the mean CD4+/CD8+ cell ratio was significantly higher in the ovalbumin group (GI) than in the ovalbumin infected (GII) or immunized (GIII) groups, which may be explained by the separate downregulation of CD4+ and upregulation of CD8+ in those groups. These data were supported by Du et al.  and De Vos et al. .
The present results showed a significant reduction in serum level of specific antiovalbumin IgE in both S. mansoni-infected (GII) and SEA-immunized (GIII) asthmatic groups compared with the pure ovalbumin group (GI). Both GII and GIII were found to have similar effects on serum antiovalbumin IgE levels. Antigen-specific IgE is known to have an important role in the pathogenesis of asthma by binding to mast cells, basophils, and eosinophils, which release inflammatory mediators upon contact with the allergen .
Similarly, Trichinella spiralis infection, Heligmosomoides polygyrus excretory secretory antigens (HES), and S. mansoni infection were associated with significant reduction in antiovalbumin IgE in murine experimental bronchial asthma. This was related to the immune-suppressive effects of T-reg cells, which were significantly increased with infection ,,.
| Conclusion|| |
All data of the present study can give a conclusion that S. mansoni infection or SEA immunization have downregulating effects on ovalbumin-induced experimental allergic airway diseases. These effects are noticed in decreasing inflammation of lung tissue, decreasing lung infiltration by CD4+cells, and decreasing allergic antibody response in the S. mansoni-infected or SEA-immunized asthmatic groups. These effects could be attributed to increased activation of T-reg cells and CD8+ cells, which downregulate the immune response.
| Acknowledgements|| |
The authors expresses their acknowledgement to Dr Noha Mohammad El Kady, Lecturer of Pathology, Faculty of Medicine, Menoufiya University, for her kind help in interpretation of pathological results.
Conflicts of interest
There are no conflicts of interest.
| Authors contribution|| |
Shimaa A. Sharaf sharing in study idea maintainence of laboratory animals, infection of mice, immunization and performance of laboratory work.
Salwa A. Shams El-Din sharing in study idea, putting protocol, sharing in laboratory work, writing, editoing and citation of the work.
Nadia S. El-Nahas, sharing in study idea, revising and editing the study.
Wafaa M. El-Kersh, sharing in study idea, revising and editing the study.
Nashaat A. Nassef, sharing in study idea, revising and editing the study.
| References|| |
Gryseels B, Polman K, Clevinx J, Kestens L. Human schistosomiasis. Lancet 2006; 368
Botros S, Sayed H, Amer N et al.
Current status of sensitivity to praziquantel in a focus of potential drug resistance in Egypt. Int J Parasitol 2005; 35
Hotez PJ, Savioli L, Fenwick A. Neglected tropical diseases of the Middle East and North Africa: review of their prevalence, distribution, and opportunities for control. PLoS Negl Trop Dis 2012; 6
Holgate ST. Mechanisms of asthma and implications for its prevention and treatment: a personal journey. Allergy Asthma Immunol Res 2013; 5
Grainge CL, Lau LC, Ward JA, et al.
Effect of bronchoconstriction on airway remodeling in asthma. N Engl J Med 2011; 364
Mortimer K, Neugebauer R, Lurmann F, et al.
Early-lifetime exposure to air pollution and allergic sensitization in children with asthma. J Asthma 2008; 45
Wahn U. The significance of environmental exposure on the progression of allergic diseases. Allergy 2011; 66
Bilenki L, Wang SH, Fan YJ, et al.
Chlamydia trachomatis infection inhibits airway eosinophilic inflammation induced by ragweed. Clin Immunol 2002; 102
Douwes J, Cheng S, Travier N, et al.
Farm exposure in utero may protect against asthma, hay fever and eczema. Eur Respir J 2008; 32
Cooper PJ. Interactions between helminth parasites and allergy. Curr Opin Allergy Clin Immunol 2009; 9
Mangan NE, Rooijen NV, McKenzie AN, Fallon PG. Helminth-modified pulmonary immune response protects mice from allergen-induced airway hyperresponsiveness. J Immunol 2006; 176
Pacífico LG, Marinho FA, Fonseca CT, et al. Schistosoma mansoni
antigens modulate experimental allergic asthma in a murine model: a major role for CD4+ CD25+ Foxp3+ T cells independent of interleukin-10. Infect Immun 2009; 77
Smits HH, Yazdanbakhsh M. Chronic helminth infections modulate allergen-specific immune responses: protection against development of allergic disorders?. Ann Med 2007; 39
Flohr C, Quinnell RJ, Britton J. Do helminth parasites protect against atopy and allergic disease?. Clin Exp Allergy 2009; 39
Liu JY, Li LY, Yang XZ, et al.
Adoptive transfer of dendritic cells isolated from helminth-infected mice enhanced T regulatory cell responses in airway allergic inflammation. Parasite Immunol 2011; 33
Caldas IR, Campi-Azevedo AC, Oliveira LFA et al.
Human Schistosomiasis mansoni
: immune responses during acute and chronic phases of the infection. Acta Trop 2008; 108
Meurs L, Labuda L, Amoah AS et al.
Enhanced pro-inflammatory cytokine responses following Toll-like-receptor ligation in Schistosoma haematobium-infected schoolchildren from rural Gabon. PLoS One 2011; 6
Herbert DR, Orekov T, Perkins C, Rothenberg ME, Finkelman FD. IL-4R alpha expression by bone marrow-derived cells is necessary and sufficient for host protection against acute schistosomiasis. J Immunol 2008; 180
Moreau E, Chauvin A. Immunity against helminths: interactions with the host and the intercurrent infections. J Biomed Biotechnol 2010; 2010
Ling EM, Smith T, Nguyen XD et al.
Relation of CD4+ CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet 2004; 363
Lopes Ida C, Santos VR, Souza VL, Rodrigues IR. Histopathological study of Schistosoma mansoni
infection in the murine model using the PC (Pará) and LILA (Maranhão) strains. Mem Inst Oswaldo Cruz 2006; 101
El-Ahwany E, Bauiomy IR, Nagy F, et al.
T regulatory cell responses to immunization with a soluble egg antigen in Schistosoma mansoni
-infected mice. Korean J Parasitol 2012; 50
Hartmann S, Schnoeller C, Dahten A, et al.
Gastrointestinal nematode infection interferes with experimental allergic airway inflammation but not atopic dermatitis. Clin Exp Allergy 2009; 39
Avwioro G. Histochemical uses of haematoxylin - a review. J Pharm Clin Sci 2011; 1
Musa D, Senocak G, Borazan G, et al.
Effects of Nigella sativa
and albendazole alone and in combination in Toxocara canis infected mice. J Pak Med Assoc 2011; 61
Zhang GQ, Han F, Fang XZ, Ma XM. CD4+, IL17 and Foxp3 expression in different pTNM stages of operable non-small cell lung cancer and effects on disease prognosis. Asian Pac J Cancer Prev 2012; 13
Lequin R. Enzyme immunoassay (EIA)/enzyme-linked immunosorbent assay (ELISA). Clin Chem 2005; 51
Morton RF, Hebel JR, Mc Carter, RJ. Medical statistics. In: Morton RF, Hebel JR, Mc Carter RJ. A study guide to epidemiology and biostatistics
(5th edition). Maryland, Gaitherburg publication; 2001;71-74.
Wan YY, Flavell RA. Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 2007; 445
Wan YY, Flavell RA. ′Yin-Yang′ functions of transforming growth factor-beta and T regulatory cells in immune regulation. Immunol Rev 2007; 220
Liu P, Li J, Yang X, Shen Y, et al.
Helminth infection inhibits airway allergic reaction and dendritic cells are involved in the modulation process. Parasite Immunol 2010; 32
Layland LE, Straubinger K, Ritter M, et al. Schistosoma mansoni
-mediated suppression of allergic airway inflammation requires patency and Foxp3(+) Treg cells. PLoS Negl Trop Dis 2013; 7
Joyce KL, Morgan W, Greenberg R, Nair MG. Using eggs from Schistosoma mansoni
as an in vivo
model of helminth-induced lung inflammation. J Vis Exp 2012; 64
Schramm G, Haas H. Th2 immune response against Schistosoma mansoni
infection. Microbes Infect 2010; 12
Tang CL, Lei JH, Wang T, et al.
Effect of CD4+ CD25+ regulatory T cells on the immune evasion of Schistosoma japonicum
. Parasitol Res 2011; 108
Choi MS, Park S, Choi T, et al.
Bee venom ameliorates ovalbumin induced allergic asthma via modulating CD4+ CD25+ regulatory T cells in mice. Cytokine 2013; 61
Akbari O, Faul JL, Hoyte EG, et al.
CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma. N Engl J Med 2006; 354
Cai XP, Zhang H, Zhang YC, et al.
Dynamics of CD4+ CD25+ T cells in spleens and mesenteric lymph nodes of mice infected with Schistosoma japonicum
. Acta Biochim Biophys Sin (Shanghai) 2006; 38
Du X, Wu J, Zhang M, et al.
Upregulated expression of cytotoxicity-related genes in IFN-g knockout mice with Schistosoma japonicum
infection. J Biomed Biotechnol 2011; 2011
Mulu A, Maier M, Liebert UG. Deworming of intestinal helminths reduces HIV-1 subtype C viremia in chronically co-infected individuals. Int J Infect Dis 2013; 17
De Vos G, Milush JM, Aaron J, et al.
Peripheral CD8+ T-cell levels are decreased in atopic wheezing children aged less than 4 years. J Investig Allergol Clin Immunol 2012; 22
Cantani A. In: Cantani A, editor. Pediatric allergy, asthma and immunology New York: Springer; 200; 732-751.
Aranzamendi C, de Bruin A, Kuiper R, et al.
Protection against allergic airway inflammation during the chronic and acute phases of Trichinella spiralis
infection. Clin Exp Allergy 2012; 43
McSorley HJ, O′Gorman MT, Blair N, et al.
Suppression of type 2 immunity and allergic airway inflammation by secreted products of the helminth Heligmosomoides polygyrus
. Eur J Immunol 2012; 42
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]