339 Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 101(Suppl. I): 339-343, 2006
Schistosoma mansoni antigen-driven interleukin-10 production in
infected asthmatic individuals
Luciana S Cardoso, Sergio C Oliveira**, Lucila GG Pacífico**, Alfredo M Góes**,
Ricardo R Oliveira, Cristina T Fonseca**, Edgar M de Carvalho/*, Maria Ilma Araújo/*/+
Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Rua João das Botas s/no,
5o andar, 40110-160 Salvador, BA, Brasil *Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brasil **Instituto de
Ciências Biológicas, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG,
and Instituto de Investigação em Imunologia (iii)/Milenio, Brasil
Asthmatics infected with Schistosoma mansoni have a less severe course of asthma and an inhibition of the Th2
inflammatory response that seems to be mediated by interleukin (IL-10). The objective of this study was to evaluate
the capacity of some S. mansoni antigens to stimulate IL-10 production in vitro by cells of asthmatic infected
individuals. Peripheral bloods mononuclear cells were stimulated with the S. mansoni recombinant antigens Sm22.6,
Sm14, P24, and PIII antigen. IL-10 was measured in the supernatants of cultures. As the recombinant antigens were
cloned in Escherichia coli, we blocked contaminant endotoxin with polymyxin B added to the cultures. We demon-
strated that all antigens used drove high production of IL-10 in S. mansoni infected individuals (n = 13, 408 ± 514
and 401 ± 383 pg/ml, 484 ± 245 pg/ml, 579 ± 468 pg/ml, respectively). In asthmatics infected with S. mansoni (n =
21) rP24 induced higher levels of IL-10 (565 ± 377 pg/ml) when compared to PIII, rSm14 and rSm22.6 (184 ± 209
pg/ml; 292 ± 243 pg/ml; 156 ± 247 pg/ml, respectively). Conclusion: the S. mansoni antigens evaluated in this study
stimulated IL-10 production by cells from infected individuals and therefore they have the potential to be used as a
modulator of the inflammatory response in asthma.
Key words: Schistosoma mansoni recombinant proteins - S. mansoni antigens - interleukin-10
Evidences has accumulated that helminth infections
protect against the development of allergy. For instance
Lynch et al. (1993) demonstrated an inhibition of the skin
prick test response to aeroallergens in individuals infected
with Ascaris lumbricoides, and that the anti-helminthic
treatment resulted in an increase in the prevalence of posi-
tive skin tests. These findings were supported by others
authors (van den Biggelaar et al. 2000) and in the last few
years some studies have demonstrated that Schistosoma
mansoni infection not only suppresses the skin prick test
response, but modulates asthma severity (Araujo et al.
2000, van den Biggelaar et al. 2000, 2001, 2004, Medeiros
et al. 2003).
Asthma is a multifatorial disease that results from ge-
netic predisposition, exposure to allergens and environ-
mental factors. While some environmental factors precipi-
tate the development of asthma, others seem to be pro-
tective. This is the case of helminth infections, particu-
larly S. mansoni, which through the modulation of the
inflammatory response prevent asthma (Medeiros et al.
2003, Araujo et al. 2004). Studying the mechanisms be-
hind the protection against allergy, Araujo et al. (2004)
found that interleukin (IL-10) seems to play an important
role in modulating the Th2 inflammatory response involved
in the pathology of allergic diseases. Supporting this idea,
Bigellar et al. showed high levels of this cytokine in indi-
viduals infected with S. haematobium who did not re-
spond to skin test to aeroallergens (van den Biggelaar et
It is well known that the acute phase of S. mansoni
infection is characterized by a strong Th1 inflammatory
response that evolues to a parasite antigen-driven Th2
response cronically (Grzych et al. 1991, Pearce et al. 1991).
It is also known that this down modulation is mediated by
S. mansoni antigen-driven IL-10 production (Sher et al.
1991). IL-10 is an anti-inflammatory cytokine produced
by a variety of cells such as macrophages, T CD4+, T
CD8+ and T CD4+CD25+ cells. While in the chronic phase
of S. mansoni infection IL-10 is produced in high levels
(Gazzinelli & Colley 1992, Williams et al. 1994, Araujo et al.
1996), in asthma, despite the immune response being the
Th2 type, the production of IL-10 is impaired. Studies have
shown that IL-10 is protective against asthma, and in-
creases in levels during immunotherapy (Akdis et al. 1998).
The protective role of IL-10 in asthma include the induc-
tion of IgG4 (Jeannin et al. 1998), down-modulation of
Th2 cytokine production (Araujo et al. 2004) and the inhi-
bition of histamine and other inflammatory mediators by
mast cells (Royer et al. 2001).
Considering the potential of S. mansoni antigens in
protecting against allergic diseases, this study aimed to
evaluate some parasite antigens regarding their ability to
induce IL-10 production. The S. mansoni antigens evalu-
ated were Sm22.6, a soluble protein from the tegument,
present in all life cycle of the worm with the exception of
egg (Jeffs et al. 1991). Sm14 is a fatty-acid binding protein
from the adult worm (Moser et al. 1991). PIII is a fraction
Financial support: CNPq, NIH grant D43TW06216, NIH/
Fogarty grant D43 TW00919
+Corresponding author: email@example.com
Received 25 May 2006
Accepted 26 June 2006
340S. mansoni antigen-driven IL-10 production • Luciana S Cardoso et al.
of S. mansoni soluble adult worm antigen (SWAP) (Hirsch
& Goes 1996). This antigen is associated with down-regu-
lation of granuloma formation in vitro (Oliveira et al. 1999)
and P24, fraction of PIII that also modulates granuloma
size in murine models (Zouain et al. 2000, 2002).
MATERIALS AND METHODS
This study evaluated the ability of some S. mansoni
antigens in inducing IL-10 production by peripheral blood
mononuclear cells (PBMC) of individuals chronically in-
fected with S. mansoni living in an endemic area in Bahia,
Brazil. It was included 34 individuals from 6 to 40 years of
age infected with S. mansoni and other helminths, such
as A. lumbricoides, Trichuris trichiura, and hookworm.
From these individuals 21 had asthma. The Table shows
demographic data and S. mansoni parasite burden in the
ng/ml) and with the mitogen phytohemaglutinin (PHA, at
a final dilution of 1:100) were used as controls. Cultures
stimulated with LPS were incubated at 37°C, 5% CO2 for 6,
12, 24, and 48 h, while cultures stimulated with S. mansoni
antigens and PHA were incubated for 48 h. After incuba-
tion, the supernatants were collected and maintained at –
20°C, for later measurement of IL-10. Levels of IL-10 were
determined by an ELISA sandwich technique, using com-
mercially available kits (R&D Systems), and the results
were expressed in picograms per milliliter based on a stan-
Addition of polymyxin B to the cultures - Suspension
of PBMC (3x106 cells/ml) were pre-incubated with Poly-
myxin B (Calbiochem, Germany) in the concentration of
10 and 20 µg/ml for 30 min at 37°C, 5% CO2. They were
then incubated with the different recombinant antigens
(10 µg/ml) or LPS (0.14 ng/ml) and the cultures were incu-
bated for 6 to 48 h as described above. Polymyxin B (10 or
20 µg/ml) was also added to cultures every 12 h.
Statistical analysis - Wilcoxon matched pairs test were
used to compare the levels of IL-10 in supernatants of
PBMC cultures with or without Polymyxin B. Kruskal-
Wallis test was used to compare the levels of Il-10 in-
duced by the different antigens. Statistical significance
was established at the 95% confidence interval.
Effect of PMB in block the effect of LPS in induce IL-
10 production - The production of IL-10 in 6, 12, 24, and
48 h-cultures stimulated with LPS in the presence or ab-
sence of PMB is shown in Fig. 1. Compared to cultures
without PMB, there was a significant reduction in the lev-
els of IL-10 by addition of this antibiotic to the cultures in
all time-points evaluated. The mean levels of IL-10 in cul-
tures without PMB were 314 ± 341 pg/ml, 469 ± 364 pg/ml
and 317 ± 378 pg/ml at 12, 24, and 48 h of cultures, and
after the addition of PMB the levels decreased to 15.6 ±
9.5 pg/ml (p = 0.06), 38 ± 55 pg/ml (p = 0.03) and 15,6 ± 9.5
pg/ml (p = 0.03). The reductions in IL-10 production in
cultures of 12, 24, and 48 h were 95.0, 91.2, and 95.1%,
Demographic data from individuals infected with Schistosoma
mansoni asthmatics and nonasthmatics
Infected subjects Asthmatic infected
(n = 13) Subjects subjects (n = 21) p value
Median age (y) 13 (6-40) 11 (6-40)> 0,05
(% of male)
58% 46.1% > 0,05
330 ± 298 52 ± 54< 0,05
The Ethical Committee of the Climério de Oliveira Hos-
pital/Federal University of Bahia approved the present
study, and an informed consent was obtained from all
study participants or their legal guardians.
S. mansoni antigens - The antigens used in this study
included three recombinant proteins, Sm22.6, Sm14, and
P24, a fraction of S. mansoni soluble adult worm antigen
(SWAP) obtained by anionic chromatography (FPLC),
named PIII, besides SWAP and SEA (soluble egg anti-
gen). The proteins were provided by the Institute of Bio-
logical Science, Departament of Biochemistry and Immu-
nology, UFMG, Brazil. The recombinant proteins were
cloned in E. coli and they were tested for lipopolysac-
charide (LPS) contamination using a commercially avail-
able LAL Chromogenic Kit (CAMBREX). The levels of
LPS were bellow 0.25 ng/ml (Sm22.6 = 0.132 ng/ml, Sm14 =
0.210 ng/ml and P24 = 0.135 ng/ml).
Cell culture and cytokine measurement - PBMC were
obtained through the Ficoll-Hypaque gradient and ad-
justed to a concentration of 3 x 106 cells/ml in RPMI 1640
containing 10% of normal human serum (AB+, heat-
inativated), 100 U/ml penicillin, 100 mg/ml streptomycin, 2
mM L-glutamine, 30 mM HEPES (all from Life technolo-
gies GIBCO BRL, Gaithersburg, MD). Cells were cultured
in vitro with antigens Sm22.6, Sm14, P24, PIII, SWAP, and
SEA (10 µg/ml) in the presence or absence of Polymyxin B
(10µg/ml) in order to neutralize the effect of LPS in induce
cytokine production. Cultures stimulated with LPS (0.15
Fig. 1: effect of Polymyxin B on LPS-induced cytokine production
in vitro. PBMCs of individuals chronically infected with Schisto-
soma mansoni (n = 6) were cultured with LPS (0.15 ng/ml) in the
presence or absence of Polymyxin B (PMB, 10 µg/ml). IL-10 was
measured using a sandwich ELISA technique. There was a signifi-
cant reduction in the levels of IL-10 when PMB was added to the
cultures (p < 0.05).
341 Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 101(Suppl. I), 2006
Polymyxin B was used in the concentration of 10 and
20 µg/ml of cultures and similar levels of reduction in
cytokine production were observed (data not shown).
Therefore, we decided to use the lower concentration of
PMB (10 µg/ml of cultures) in cultures stimulated with S.
mansoni recombinant antigens. We tested the viability of
cells in cultures with Polymyxin B using trypan blue stain
and observed that the viability was about 98%.
Production of IL-10 in cultures stimulated with S.
mansoni antigens - The IL-10 production induced by S.
mansoni antigens is shown in Fig. 2. We observed that all
antigens evaluated in this study induced IL-10 produc-
tion in infected individuals (Fig. 2A). The level of this
cytokine were 408 ± 514 pg/ml to rSm22.6, 401 ± 383 pg/ml
to rSm14, 484 ± 245 pg/ml to PIII and 579 ± 468 pg/ml to
rP24 antigen. There was no significant difference in the
levels of IL-10 induced by the different antigens (p > 0,05).
In cultures stimulated with SWAP and SEA the levels of
IL-10 were 140 ± 291 pg/ml and 46 ± 43 pg/ml, respec-
Fig. 2B shows the levels of IL-10 production in asth-
matic infected individuals. Similarly, all antigen induced
IL-10 production. The levels of this cytokine in cultures
stimulated with rSm22.6, rSm14, PIII, and rP24 were 156 ±
247 pg/ml, 292 ± 243 pg/ml, 184 ± 209 pg/ml, and 565 ± 377
pg/ml. The antigen rP24 induced higher levels of IL-10
compared to the other antigens (p < 0.05). All antigens
induced higher levels of IL-10 in comparison with SWAP
and SEA (p < 0,001).
Levels of IL-10 were below the detection limit in un-
stimulated cultures, and these cytokines were detected in
high levels (≥ 1500 pg/ml) in the supernatants of PBMC
cultures stimulated with PHA (not shown).
S. mansoni infection seems to be protective against
asthma (Medeiros et al. 2003, Araujo et al. 2004). Using
mice models of S. mansoni infection it has been demon-
strated that this parasite also protects against the devel-
opment of auto-immune disease such as diabetes, experi-
mental auto-immune encephalopathy, and Crohn’s disease
(Cooke et al. 1999, Elliott et al. 2003, La Flamme et al. 2003,
Sewell et al. 2003, Zaccone et al. 2003). Some of these
studies suggest that IL-10 is a key cytokine involved in
the modulation of the inflammatory immune response ob-
served in these diseases. IL-10 is produced by cells of
individuals chronically infected with S. mansoni and there
are some S. mansoni antigens able to induce IL-10 pro-
duction in vitro. On the other hand, there is impaired pro-
duction of IL-10 in asthmatic individuals, even when their
cells are stimulated in vitro with dust mite antigens (Araujo
et al. 2004) and LPS (Borish et al. 1996, Tomita et al. 2002).
In this study we evaluated the ability of some schisto-
some vaccine candidate antigens, ie, Sm14, Sm 22.6, p24,
and PIII in induce IL-10 production by cells from asth-
matic infected individuals. Some of these antigens pro-
tect mice against liver fibrosis, the major pathology asso-
ciated with schistosomiasis, and induce IL-10 production
in individuals chronically infected with S. mansoni (Brito
et al. 2000, Zouain et al. 2000, Pacifico et al. 2006). Contrib-
uting to the choice of these antigens is the fact that they
are proteins from the tegument and do not cross react
with egg antigens, that are known to be involved in the
pathogenesis of schistosomiasis (Simpson et al. 1990).
All S. mansoni antigens used in this study induced
high levels of IL-10 by cells of individuals chronically
infected with the parasite, p24 being the major inductor of
this cytokine in asthmatic infected individuals.
Due the fact that the antigens Sm14, Sm22.6, and p24
used in this study were recombinantly cloned in E. coli,
Polymyxin B was added to the cell cultures to block the
effect of endotoxin to stimulate IL-10 production. Indeed,
the use of Polymyxin B in control cultures stimulated with
LPS completely abrogated IL-10 production. As the anti-
gens used in this study have the ability to induce IL-10
and are possibly capable of modulating the inflammatory
immune response, they may be produced in a non-bacte-
rial vector for future use as vaccines or treatment to cer-
tain immunologic-based disorders.
It is known that during S. mansoni infection cells from
the innate immune response, T cells and T regulatory cells
are able to produce IL-10 (Hesse et al. 2004). There are
some S. mansoni antigens described in the literature, such
as LNFPIII (Okano et al. 2001, Thomas et al. 2003) and
fosfatidilserine (PS) (van der Kleij et al. 2004) that also
induce IL-10 production by the cells from the innate im-
Fig. 2: production of IL-10 by PBMCs of individuals chronically infected with Schistosoma mansoni stimulated in vitro with S. mansoni
antigens (10 µg/ml). IL-10 was measured in 48 h culture supernatants using a sandwich ELISA technique. A: production of IL-10 in S.
mansoni infected individuals. The antigens rSm22.6, rSm 14, PIII, and P24 induced higher levels of IL-10 compared to SWAP and SEA (p
< 0.05); B: production of IL-10 by cells from asthmatics infected with S. mansoni. The antigens rSm22.6, rSm 14, PIII, and P24 also
induced higher levels of IL-10 compared to SWAP and SEA (p < 0.05). Levels of IL-10 in cultures stimulated with p24 were higher than
the levels observed when the cells were stimulated with rSm22.6, rSm14, and PIII (p < 0.05; denoted by an asterisk).
342S. mansoni antigen-driven IL-10 production • Luciana S Cardoso et al.
mune system. We are currently evaluating if the S. mansoni
antigens used in this study are able to induce IL-10 by
cells from uninfected asthmatics. These studies may re-
sult in new strategies to prevent allergic diseases.
To Charlton Cley Barros Castro for technical support, Elbe
Myrtes for the secretarial assistance, and Dr Daniel Morgan for
the corrections and suggestions made in the text.
Akdis CA, Blesken T, Akdis M, Wuthrich B, Blaser K 1998.
Role of interleukin 10 in specific immunotherapy. J Clin
Invest 102: 98-106.
Araujo MI, de Jesus AR, Bacellar O, Sabin E, Pearce E, Carvalho
EM 1996. Evidence of a T helper type 2 activation in hu-
man schistosomiasis. Eur J Immunol 26: 1399-1403.
Araujo MI, Hoppe B, Medeiros M, Jr., Alcantara L, Almeida
MC, Schriefer A, Oliveira RR, Kruschewsky R, Figueiredo
JP, Cruz AA, Carvalho EM 2004. Impaired T helper 2
response to aeroallergen in helminth-infected patients with
asthma. J Infect Dis 190: 1797-1803.
Araujo MI, Lopes AA, Medeiros M, Cruz AA, Sousa-Atta L,
Sole D, Carvalho EM 2000. Inverse association between
skin response to aeroallergens and Schistosoma mansoni
infection. Int Arch Allergy Immunol 123: 145-148.
Borish L, Aarons A, Rumbyrt J, Cvietusa P, Negri J, Wenzel S
1996. Interleukin-10 regulation in normal subjects and pa-
tients with asthma. J Allergy Clin Immunol 97: 1288-1296.
Brito CF, Caldas IR, Coura Filho P, Correa-Oliveira R, Oliveira
SC 2000. CD4+ T cells of schistosomiasis naturally resis-
tant individuals living in an endemic area produce inter-
feron-gamma and tumour necrosis factor-alpha in response
to the recombinant 14KDA Schistosoma mansoni fatty acid-
binding protein. Scand J Immunol 51: 595-601.
Cooke A, Tonks P, Jones FM, O’Shea H, Hutchings P, Fulford
AJ, Dunne DW 1999. Infection with Schistosoma mansoni
prevents insulin dependent diabetes mellitus in non-obese
diabetic mice. Parasite Immunol 21: 169-176.
Elliott DE, Li J, Blum A, Metwali A, Qadir K, Urban Jr JF,
Weinstock JV 2003. Exposure to schistosome eggs protects
mice from TNBS-induced colitis. Am J Physiol Gastrointest
Liver Physiol 284: G385-391.
Gazzinelli G, Colley DG 1992. Human immune responses dur-
ing schistosomiasis mansoni. Rev Soc Bras Med Trop 25:
Grzych JM, Pearce E, Cheever A, Caulada ZA, Caspar P, Heiny
S, Lewis F, Sher A 1991. Egg deposition is the major stimu-
lus for the production of Th2 cytokines in murine schisto-
somiasis mansoni. J Immunol 146: 1322-1327.
Hesse M, Piccirillo CA, Belkaid Y, Prufer J, Mentink-Kane M,
Leusink M, Cheever AW, Shevach EM, Wynn TA 2004.
The pathogenesis of schistosomiasis is controlled by coop-
erating IL-10-producing innate effector and regulatory T
cells. J Immunol 172: 3157-3166.
Hirsch C, Goes AM 1996. Characterization of fractionated
Schistosoma mansoni soluble adult worm antigens that elicit
human cell proliferation and granuloma formation in vitro.
Parasitology 112 (Pt 6): 529-535.
Jeannin P, Lecoanet S, Delneste Y, Gauchat JF, Bonnefoy JY
1998. IgE versus IgG4 production can be differentially regu-
lated by IL-10. J Immunol 160: 3555-3561.
Jeffs SA, Hagan P, Allen R, Correa-Oliveira R, Smithers SR,
Simpson AJ 1991. Molecular cloning and characterisation
of the 22-kilodalton adult Schistosoma mansoni antigen
recognised by antibodies from mice protectively vaccinated
with isolated tegumental surface membranes. Mol Biochem
Parasitol 46: 159-167.
La Flamme AC, Ruddenklau K, Backstrom BT 2003. Schisto-
somiasis decreases central nervous system inflammation
and alters the progression of experimental autoimmune en-
cephalomyelitis. Infect Immun 71: 4996-5004.
Lynch NR, Hagel I, Perez M, Di Prisco MC, Lopez R, Alvarez
N 1993. Effect of anthelmintic treatment on the allergic
reactivity of children in a tropical slum. J Allergy Clin
Immunol 92: 404-411.
Medeiros M Jr, Figueiredo JP, Almeida MC, Matos MA, Araujo
MI, Cruz AA, Atta AM, Rego MA, de Jesus AR, Taketomi
EA, Carvalho EM 2003. Schistosoma mansoni infection is
associated with a reduced course of asthma. J Allergy Clin
Immunol 111: 947-951.
Moser D, Tendler M, Griffiths G, Klinkert MQ 1991. A 14-
kDa Schistosoma mansoni polypeptide is homologous to a
gene family of fatty acid binding proteins. J Biol Chem 266:
Okano M, Satoskar AR, Nishizaki K, Harn Jr DA 2001. Lacto-
N-fucopentaose III found on Schistosoma mansoni egg an-
tigens functions as adjuvant for proteins by inducing Th2-
type response. J Immunol 167: 442-450.
Oliveira DM, Gustavson S, Silva-Teixeira DN, Goes AM 1999.
Nitric oxide and IL-10 production induced by PIII – A frac-
tion of Schistosoma mansoni adult worm antigenic prepa-
ration – associated with downregulation of in vitro granu-
loma formation. Hum Immunol 60: 305-311.
Pacifico LG, Fonseca CT, Chiari L, Oliveira SC 2006. Immuni-
zation with Schistosoma mansoni 22.6 kDa antigen induces
partial protection against experimental infection in a re-
combinant protein form but not as DNA vaccine. Im-
munobiology 211: 97-104.
Pearce EJ, Caspar P, Grzych JM, Lewis FA, Sher A 1991.
Downregulation of Th1 cytokine production accompanies
induction of Th2 responses by a parasitic helminth, Schis-
tosoma mansoni. J Exp Med 173: 159-166.
Royer B, Varadaradjalou S. Saas P, Guillosson JJ, Kantelip JP,
Arock M 2001. Inhibition of IgE-induced activation of hu-
man mast cells by IL-10. Clin Exp Allergy 31: 694-704.
Sewell D, Qing Z, Reinke E, Elliot D, Weinstock J, Sandor M,
Fabry Z 2003. Immunomodulation of experimental autoim-
mune encephalomyelitis by helminth ova immunization.
Int Immunol 15: 59-69.
Sher A, Fiorentino D, Caspar P, Pearce E, Mosmann T 1991.
Production of IL-10 by CD4+ T lymphocytes correlates
with down-regulation of Th1 cytokine synthesis in helm-
inth infection. J Immunol 147: 2713-2716.
Simpson AJ, Hagan P, Hackett F, Omer Ali P, Smithers SR
1990. Epitopes expressed on very low Mr Schistosoma
mansoni adult tegumental antigens conform to a general
pattern of life-cycle cross-reactivity. Parasitology 100 Pt
343 Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 101(Suppl. I), 2006
Thomas PG, Carter MR, Atochina O, Da’Dara AA, Piskorska
D, McGuire E, Harn DA 2003. Maturation of dendritic cell
2 phenotype by a helminth glycan uses a Toll-like receptor
4-dependent mechanism. J Immunol 171: 5837-5841.
Tomita K, Lim S, Hanazawa T, Usmani O, Stirling R, Chung
KF, Barnes PJ, Adcock IM 2002. Attenuated production of
intracellular IL-10 and IL-12 in monocytes from patients
with severe asthma. Clin Immunol 102: 258-266.
van den Biggelaar AH, Lopuhaa C, van Ree R, van der Zee JS,
Jans J, Hoek A, Migombet B, Borrmann S, Luckner D,
Kremsner PG, Yazdanbakhsh M 2001. The prevalence of
parasite infestation and house dust mite sensitization in
Gabonese schoolchildren. Int Arch Allergy Immunol 126:
van den Biggelaar AH, Rodrigues LC, van Ree R, van der Zee
JS, Hoeksma-Kruize YC, Souverijn JH, Missinou MA,
Borrmann S, Kremsner PG, Yazdanbakhsh M 2004. Long-
term treatment of intestinal helminths increases mite skin-
test reactivity in Gabonese schoolchildren. J Infect Dis 189:
van den Biggelaar AH, van Ree R, Rodrigues LC, Lell B, Deelder
AM, Kremsner PG, Yazdanbakhsh M 2000. Decreased
atopy in children infected with Schistosoma haematobium:
a role for parasite-induced interleukin-10. Lancet 356: 1723-
van der Kleij D, van den Biggelaar AH, Kruize YC, Retra K,
Fillie Y, Schmitz M, Kremsner PG, Tielens AG, Yaz-
danbakhsh M 2004. Responses to Toll-like receptor ligands
in children living in areas where schistosome infections are
endemic. J Infect Dis 189: 1044-1051.
Williams ME, Montenegro S, Domingues AL, Wynn TA,
Teixeira K, Mahanty S, Coutinho A, Sher A 1994. Leuko-
cytes of patients with Schistosoma mansoni respond with
a Th2 pattern of cytokine production to mitogen or egg
antigens but with a Th0 pattern to worm antigens. J Infect
Dis 170: 946-954.
Zaccone P, Fehervari Z, Jones FM, Sidobre S, Kronenberg M,
Dunne DW, Cooke A 2003. Schistosoma mansoni antigens
modulate the activity of the innate immune response and
prevent onset of type 1 diabetes. Eur J Immunol 33: 1439-
Zouain CS, Gustavson S, Oliveira SC, Azevedo V, Alves JB,
Goes AM 2000. The role of IL-10 and IgG1 in the protec-
tion and granulomatous response in Schistosoma mansoni
P24-immunized mice. Vaccine 19: 1218-1224.
Zouain CS, Gustavson S, Silva-Teixeira DN, Contigli C,
Rodrigues Jr V, Leite MF, Goes AM 2002. Human immune
response in schistosomiasis: the role of P24 in the modula-
tion of cellular reactivity to Schistosoma mansoni antigens.
Hum Immunol 63: 647-656.