Autoimmunity, January 2009; 42(1): 25–32

q Informa Healthcare USA, Inc.

ISSN 0891-6934 print/1607-842X online
DOI: 10.1080/08916930802228290

Spontaneous arthritis in MRL/lpr mice is aggravated by Staphylococcus

aureus and ameliorated by Nippostrongylus brasiliensis infections

MARIO C. SALINAS-CARMONA1, GUADALUPE DE LA CRUZ-GALICIA1,

ISABEL PÉREZ-RIVERA1, JUAN M. SOLÍS-SOTO1, JUAN C. SEGOVIANO-RAMIREZ1,
ANNA VELIA VÁZQUEZ1, & MARIO A. GARZA2
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1
Department of Immunology, Faculty of Medicine and University Hospital, Monterrey, Mexico, and 2Rheumatology Service,
Faculty of Medicine and University Hospital, Monterrey, Mexico

(Submitted 19 January 2008; accepted 20 May 2008 )

Abstract
Rheumatoid arthritis is an autoimmune disease that affects human beings worldwide. Infections have been associated to
autoimmune diseases because their ability to induce a dominant cytokine response. Joint inflammation has been related
to Th1 response because they induce high expression of proinflammatory cytokines TNF-a, IL-1, IFN-g. MRL/lpr mice
spontaneously develop an autoimmune disease affecting joints, kidneys, etc. We compared incidence and severity of arthritis,
For personal use only.

antibody response, cytokine production, in mice infected with bacteria or helminthes in the Murphy Roths Large (MRL)lpr
mice. Infections with helminthes Heligmosomoides polygyrus, Nippostrongylus brasiliensis or bacteria Nocardia brasiliensis and
Staphylococcus aureus were studied. IL-4, IFN-g and IgG1, IgG2a antibody productions were determined. IFN-g was
increased in all groups, the highest production was observed after bacterial infection; IL-4 production was higher after
helminthes infection. IgG1 sera levels were increased in the helminthes infected group. IgG2a sera concentration was
stimulated by bacterial infection. The histopathology showed that 100% of bacterial infected mice developed arthritis and
severe tissue damage such as cartilage erosion and bone destruction. Animals infected with parasites showed a decreased
incidence and severity of arthritis. Severity of tissue damage in joints is correlated with increased numbers of lymphocytes and
macrophages immunoreactive to proinflammatory cytokines.

Keywords: Arthritis, bacteria, cytokines, infections, parasites

Introduction Rheumatoid arthritis is less frequent in certain

Autoimmune diseases are related to genetic suscepti-
bility and environmental factors such as virus and
bacterial infections. Diseases such as rheumatoid
arthritis, lupus erythematosus, type 1 diabetes mellitus,
multiple sclerosis, etc., are associated with microbial
infections [1,2]. Molecular mimicry, super antigen
induction or adjuvant-induced stimulation of the
immune system are some of the proposed mechanisms
to explain the microbe aetiology of autoimmune diseases
[3]. However, recently it has been published that
infection may have beneficial effects on the subsequent
development of the autoimmune disease [4].
geographic areas such as tropical countries with a high
incidence of infectious diseases, and in particular of
parasitic infections [5]. Helminthes are parasites with
the ability to affect the immune system and down-
regulate the immune responses in the body. These
parasites promote Th2 responses associated with
production of IL-4 and IL-13 [6–8]. Helminthes can
trigger Th2 responses that help to limit the worm
number in the host, but may attenuate excessive Th1-
type inflammation promoting the production of power-
ful immunomodulatory molecules such as IL-10 and

Correspondence: M.C. Salinas-Carmona, Gonzalitos 235 Colonia Mitras, Monterrey, NL 64460, Mexico. Tel: 52 81 83 33 1058.
Fax: 52 81 83 33 1058. E-mail: msalinas@hu.uanl.mx
 26 M. C. Salinas-Carmona et al.
tumor growth factor beta (TGF-b) [9,10]. These
changes in immune responsiveness can persist long after
elimination of these parasites [11]. Even more, some
helminthes or their antigens have been employed as a
therapeutic approach in autoimmune disorders [12].
Infection of mice with intestinal nematode parasites,
such as Heligmosomoides polygyrus and Nippostrongylus
brasiliensis, induce a strong Th2 immune response with
an increase in IL-4 and IL-13 [10,11]. Murphy and
Roths [13] reported that the MRL/lpr mice showed a
spontaneous rheumatoid arthritis-like disease towards
the end of their life span. They reported that the large
and small joints of the hind limbs of female mice affected
with spontaneous arthritis showed synovial cell prolifer-
ation, pannus formation, cartilage erosion, and bone
destruction [14,15].
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The histopathological similarities between human
rheumatoid synovitis and arthritis of MRL/lpr mice,
and the presence of rheumatoid factors make this
mouse strain a good model to study the human
rheumatoid arthritis [14]. Previous studies using this
mice strain demonstrated that the autoimmune
disease developed in these animals is associated with
an increase of serum antibodies, in particular IgG2a
[16]. Other studies demonstrated that an increase in
Th1 cytokines, particularly IFN-g, appeared to be an
For personal use only.
essential factor for damage development [17,18].
Although little is known about the arthropathy in this
mouse model, the destructive joint damage appeared
to be accelerated by Freund’s adjuvant injection [19].
It is accepted that the bacteria infection induces a Th1
response and that helminthes stimulate mainly a Th2
cytokine response.
In this study, we evaluated the immune response of
MRL/lpr mice infected with helminthes or bacteria,
and showed that these infections affect the develop-
ment of the spontaneous arthritis. The Gram-positive
bacteria increased tissue damage in affected joints and
the parasites diminished the incidence and severity of
arthritis in these mice, these findings correlate with
increased number of immunoreactive cells to Th1
cytokines.
Material and methods
Animals
Twelve-week-old female MRL/lpr mice were obtained
from The Jackson Laboratory (Bar Harbor, ME, USA)
and were maintained under standard conventional
conditions with autoclaved food and sterile water ad
libitum. Requirements for care and handling of
experimental animals according to international and
Mexican regulations (NOM-062-Z00-1999) were met.
Blood samples were obtained from mice on days 0,
21 and 42 after their infection. Sera for enzyme-linked
immunosorbent assays (ELISA) were stored at 2708C
until use.
All mice were examined every other day looking for
arthritis signs, which included erythema, joint swelling
and mobility during 45 days after infection. Arthritis
was scored as moderate when inflammation was
present but no erythema and severe if erythema was
also present in addition of inflammation.
Infection with parasites. MRL/lpr mice were infected
orally with 200 third-stage larvae (L3) of H. polygyrus, or
subcutaneously (s.c.) with 500 L3 of Nippostrongylus
brasiliensis (helminthes were kindly donated by Dr J.F.
Urban, Department of Agriculture, Beltsville, MD,
USA).
Infection with bacteria. MRL/lpr mice were injected sc. in
the thorax with either Nocardia brasiliensis 8 £ 108
CFU/ml or Staphylococcus aureus 1 £ 108 CFU/ml [20].
Determination of IgG1 and IgG2a antibodies in sera from
mice infected with Nocardia brasiliensis and S. aureus
IgG1 and IgG2a anti-Nocardia brasiliensis antibodies
were determined by an ELISA technique as previously
published. Briefly, Nocardia brasiliensis was cultured in
1 l Erlenmeyer flasks with 170 ml of brain heart
infusion broth (Difco Laboratories, Detroit, MI,
USA) for 7 days at 378C. Bacterial mass was extensively
washed with distilled water and defatted with ethanol –
ethylic ether. Protein antigens were extracted with
0.01 M Tris – HCl containing 0.01 M magnesium
acetate by stirring, the supernatant was obtained by
ultracentrifugation and later dialysed. Protein concen-
tration was determined by Bradford assay [21]. This
antigen is named the crude cellular extract (CCE). We
used Costar plates (Corning, NY, USA) that were
coated with CCE antigen, 0.5 mg per well overnight at
48C. After washing with phosphate-buffered saline-T
(PBS-T), serum samples were diluted 5-fold and
incubated for 60 min at 378C. IgG subclasses were
measured using goat anti-mouse IgG1 and IgG2a–
horse raddish peroxidase (HRP) (Southern Biotech,
Birmingham, AL, USA), followed by o-phenylenedia-
mine dihydrochloride (OPD) peroxidase substrate
(Sigma, St Louis, MO, USA). The optical densities
were measured with a microplate reader at 492 nm.
For S. aureus infected mice, we set up an ELISA, to
determine anti-S. aureus antibodies which included
the IgG1 and IgG2a antibodies. Briefly, 96-wells
Costar plates were coated with 0.05 mg of S. aureus
Cowan A protein (Sigma) in acetate buffer (pH 5.0)
per well overnight at 48C. After washing with PBS-T,
the unbound sites on the plastic surface were blocked
with PBS containing 5% skim milk for 2 h at 378C.
The plates were washed five times with PBS-Tat room
temperature and mice serum was diluted 1:2500 in
PBS-T. Five percentage skim milk was added to each

well and the plate was kept at 378C for 1 h. After
washing five times, anti-mouse IgG1 – HRP and
IgG2a – HRP conjugate, diluted in PBS-T containing
1% skim milk, were added and incubated at 378C for
1 h. After washing 100 ml of OPD peroxidase substrate
(Sigma) was added to each well. After 30 min at room
temperature, the reaction was stopped with 40 ml of
1 N H2SO4. The plates were read in an automated
ELISA reader (Sunrise, Tecan, Grödig, Austria) at
492 nm. The results of the assay are expressed as mean
of milligram concentration in serum of duplicate
determinations.
Determination of IgG1 and IgG2a antibodies in serum
of mice infected with the parasites H. polygyrus and
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Nippostrongylus brasiliensis
IgG1 and IgG2a anti-H. polygyrus antibodies were
assayed by ELISA. H. polygyrus and Nippostrongylus
brasiliensis antigens were prepared from adult worms
obtained 7 days after inoculating L3 into BALB/c
mice (the parasites cycle were maintained in BALB/c
mice). Worms were isolated by the Baermann
procedure as described previously [8] in summary,
parasites were washed several times in Roswell Park
Memorial Institute (RPMI) 1640 containing
For personal use only.
100 U/ml penicillin, 100 mg/ml streptomycin,
2.5 mg/ml gentamicin and 10 mg/ml funfazone, and
incubated for 10 days in 24-well culture plates at
100 – 200 worms/well. Culture fluids were collected
every other day and concentrated 50 –100-fold with a
10,000 MW cut-off Amicon membrane. Protein
concentration was determined by Bradford [21]
assay. Immulon II microtiter plates (Dynatech,
Chantilly, VA, USA) were coated with secretory –
excretory antigen, 0.25 mg/well and incubated over-
night at 48C, respectively. After washing with PBS-T,
serum samples were diluted 5-fold and incubated for
60 min at 378C. IgG subclasses were measured using
goat anti-mouse IgG1 and IgG2a –HRP (Southern
Biotech) and OPD peroxidase as chromogen-sub-
strate (Sigma). Results of duplicate determinations
are presented as mean values in milligram
concentration.
Cytokine determinations by ELISA
IFN-g and IL-4 were quantified by an ELISA
technique according to the manufacturer’s instruc-
tions (Pierce Endogen, Rockford, IL, USA). Briefly,
in the case of IFN-g, 50 ml of standards containing 0,
37, 111, 333, 1000 and 3000 pg/ml, or mice sera
diluted 1:10 were added to each well in duplicate and
incubated for 2 h at room temperature. After three
washings, we added 50 ml of biotinylated antibody and
washed again, then the streptavidin –HRP solution
was added. We used tetramethylbenzidine (TMB) as
substrate. The optical densities were measured with a
Infection affects arthritis severity 27
microplate reader at 492 nm. The results were
calculated using curve-fitting statistical software
(GraphPad Prism 4).
For IL-4 determination, we used 50 ml of standards
containing: 0, 15, 75 and 375 pg/ml, or mice sera
diluted 1:5 in duplicate. Plates were then incubated
for 2 h at 378C. A conjugated reagent followed by
TMB substrate was added. The optical densities were
measured with a microplate reader at 492 nm. The
results were calculated using curve-fitting statistical
software (GraphPad Prism 4).
Histological evaluation and damage score
Mice were killed by cervical dislocation 45 days after
infection with bacteria or parasites. The limb joints
were fixed in 10% buffered formalin and decalcified
in 10% nitric acid in 70% ethanol for 48 h and
processed for paraffin embedding. Thick sections
(4 mm) were stained with haematoxylin and eosin.
Histopathological alterations of the joints were scored
by a pathologist using a ranking system modified from
Hom [22]. Briefly, the joints were evaluated looking
for the presence of: (1) synovial inflammation, (2)
synovial hyperplasia, (3) pannus formation, (4)
cartilage erosion, and (5) bone destruction; the
arthritis severity was graded according to the articular
damage detected, as follows: þ 1 ¼ subsynovial
inflammation, þ 2 ¼ subsynovial inflammation þ
synovial hyperplasia, þ 3 ¼ subsynovial inflamma-
tion þ synovial hyperplasia þ pannus formation and
þ 4 ¼ subsynovial inflammation þ synovial hyper-
plasia þ pannus formation þ cartilage erosion and
bone destruction. Only maximum score of tissue
damage was recorded for each animal.
Immunocytochemistry
Tissue of the joint was fixed in 4% paraformaldehyde
in 0.2 M PBS pH 7.4 overnight. Paraffin serial
sections of tissue with a thickness of 10 mm were
made. Endogenous peroxidase was depleted by using
0.3% hydrogen peroxide in methanol. After washing,
immunocytochemistry was performed using polyclo-
nal antibodies (Santa Cruz Biotechnology, Inc., CA,
USA) against mouse IL-1b (sc-1252 goat), mouse IL-4
(sc-1260 goat), mouse IL-6 (sc-1265 goat), mouse IL-
10 (sc-1783 goat), mouse IFN-g (sc-9344 goat),
mouse TGF-b (sc-146 goat), and mouse TNF-a (sc-
1349 goat). They were used at a dilution of 1:500 in
PBS pH 7.4 with 0.5% Triton-X-100 (PBS –TX100)
and incubated overnight at 48C. After repeated
washes, sections were incubated for 2 h at room
temperature with a second antibody against goat IgG
labelled with HRP (sc-2922 rabbit, Santa Cruz
Biotechnology, Inc.) in PBS – TX100.
The peroxidase was developed using 0.05% 3, 3-
diaminobenzidine tetrahydroxychloride (Sigma) in
 28 M. C. Salinas-Carmona et al.
PBS buffer pH 7.4 containing 0.01% hydrogen
peroxide. Counterstaining was performed with
haematoxylin.
Morphometrical analysis. It was performed using serial
sections; the serial areas with different cytokine
staining were analysed. Counts of immunoreactive
cells were performed in five adjacent fields ( £ 400) at
inflammation site. Negative controls included
omission of the primary antibody, liquid-phase
absorption with the homologous antigen (Santa
Cruz Biotechnology, Inc.), and use of non-immune
serum. Sections of the spleen, on the same slide, were
also examined to act as positive controls.
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Statistical analysis
2
*Statistical significance p # 0.05 was calculated by x
for histopathological study and Krusal Wallis test for
antibodies, cytokines, and proteinuria (SPSS software).
Results
Clinical evaluation
The arthritis clinical evaluation was scored weekly.
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In Figure 1, we present a photograph of a mouse
before developing arthritis and a typical case of
inflamed joint with erythema and swelling after being
injected with S. aureus.
Histological analysis to evaluate incidence and severity
of spontaneous arthritis in MRL/lpr mice
The MRL/lpr mice infected with S. aureus, presented
higher severity of bone destruction and higher
incidence of arthritis compared to the helminthes
infected group as presented in Table I. The incidence
of arthritis was at 100% in the infected mice with
bacteria either Nocardia brasiliensis or S. aureus
compared to a 70% presented in the parasites infected
group. Severity of tissue damage was graded by
microscopic examination of affected joints, cartilage
Figure 1. Arthritis clinical evaluation in the MRL/lpr mice: (A)
normal and (B) inflammation with erythema in a mouse infected
with S. aureus.
and bone destruction being the maximum expression
of tissue lesion. Some mice presented inflammation
and pannus, others presented cartilage destruction
and synovial hyperplasia, but in all cases the recorded
data were considering only the maximum damage.
The bone destruction damage was aggravated by
S. aureus infection, compared to mice infected with
helminthes differences among these groups were
statistically significant with p , 0.009.
Immunocytochemistry
Immunocytochemical analysis showed a very strong
difference in the amount of immunoreactive cells to
Il-1b and Il-12 compared with control mouse as
presented in Figure 2. Larger amount of lymphocytes
and macrophages were immunoreactive to proinflam-
matory cytokines in the connective tissue of the joints
of infected mice with S. aureus. The Figure 2B shows
the immunoreactive cells to IL-1b and Figure 2C
shows the immunoreactive cells to IL-12 in infected
mice with Nocardia brasiliensis. In contrast, mice
infected with helminthes presented less immuno-
reactive cells to these cytokines.
Morphometrical analysis
The quantitification of immunoreactive cells to IL-1b
and IL-12 was higher in infected mice with S. aureus
than in the other two groups as presented in Figure 3.
Same findings were observed with TNF-a and IFN-g.
Figure 3 shows statistically significant difference
between infected and non-infected groups, although
quantity immunoreactive cells of group infected with
Nocardia brasiliensis was lesser than S. aureus infected
one.
Enhanced serum levels of IgG1 in MRL/lpr mice infected
with helminthes
An increased level of IgG1 anti-H.p antibodies was
seen in 21 and 42 days after mice infection as shown in
Figure 4. Determination of IgG2a anti-H. polygyrus
presented no significant changes after infection. Sera
levels of IgG1 anti- Nippostrongylus brasiliensis were
significantly higher in 21 and 42 days after infection. A
slight increase between 0 and 42 days sera levels was
observed in IgG2a anti-Nippostrongylus brasiliensis
antibodies. On the other hand, S. aureus infected
mice induced a significant change in IgG2a sera levels,
21 and 42 days after infection, and only little
variations in IgG1 levels. In the case of infection
with Nocardia brasiliensis, the IgG1 levels of anti-
Nocardia brasiliensis antibodies showed a significant
variation but more intense in concentrations of IgG2a
specific antibodies as presented in Figure 4. Each data
point shows the mean (^ SE) of at least 10 animals
per group and is representative of two replicate
 Infection affects arthritis severity 29

Table I. Incidence and severity of spontaneous arthritis in infected MRL/lpr mice compared with control mice.

Infectious agent

Bacteria Helminthes

Tissue lesion Control Nocardia brasiliensis S. aureus H. polygyrus Nippostrongylus brasiliensis

9/10 11/11 10/10 7/10 7/10

Severity of arthritis
Synovial inflammation 1/10 1/11 0/10 0/10 0/10
Synovial hyperplasia 3/10 4/11 0/10 4/10 1/10
Pannus formation 0/10 0/11 1/10 1/10 1/10
Cartilage erosion 4/10 5/11a 3/10a 1/10 4/10
Bone destruction 1/10 1/11a 6/10a 1/10 1/10

*The joints were evaluated looking for the presence of: synovial inflammation, synovial hyperplasia, pannus formation, cartilage erosion and
bone destruction. Each group included 10 mice for helminthes and control groups and 11 for group infected with Nocardia brasiliensis.
a
*Differences in bone destruction between groups were statistically significant ¼ ( p , 0.009).
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experiments; an asterisk indicates values that are
statistically significant with differences from the day 0
at the beginning of the experiment p , 0.001.
IFN-g and IL-4 were augmented in MRL/lpr mice
infected with bacteria and helminthes, respectively
Control MRL/lpr mice receiving no infectious agents
were used as control for cytokine quantification. An
increase in the concentration of IFN-g was seen in all
For personal use only.
the infection compared to control mice, but the most
significant increase in IL-4 levels, were found in the
sera from MRL/lpr mice infected with H. polygyrus or
Nippostrongylus brasiliensis parasites.
The changes in concentration of IL-4 and IFN-g
levels were statistically significant p , 0.0001 and
p , 0.05, respectively. Results are presented as the
mean (^ SE) of at least 10 animals per group and are
representative of duplicate measurements.

infected mice that received either bacteria or parasites.

Discussion
It is interesting that the highest level of IFN-g was
induced by S. aureus as presented in Table II. On the We used the MRL/lpr mice to test if the spontaneous
other hand, IL-4 levels, augmented in all groups after arthritis could be modified with bacterial and

Figure 2. Microscopy images of the joint of the knee. (A) Normal joint in a control mouse without infection (bar ¼ 200 mm). (B) Joint of a
mouse infected with S. aureus (bar ¼ 1.2 mm). (C) Immunoreactive cells to IL-1b in the connective tissue in the region of the joint of a mouse
infected with S. aureus (bar ¼ 200 mm) and (D) immunoreactive cells to IL-12 in the connective tissue in the region of the joint of a mouse
infected with Nocardia brasiliensis (bar ¼ 80 mm).
 30 M. C. Salinas-Carmona et al.
Figure 3. Count of immunoreactive cells to IL-1b, TNF-a, IFN-g
and IL-12 cytokines, by morphometrical analysis in tissue slides of
the foot pad from infected BALB/c mice.
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helminthes infections. Infected mice with either
pathogen showed significantly increased levels of IL-4
and IFN-g cytokines compared to control-uninfected
animals. S. aureus infection promoted a clearly
predominant Th1 response in the MRL/lpr mice as
indicated by the significant increase of serum IFN-g
and IgG2a anti-S. aureus antibodies. This result was
expected since the S. aureus Cowan strain express the
super antigen A protein and it is well known that it
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plays an important role in this bacteria pathogenicity.
It is also known that protein A induces a high
production of IgG2a antibodies [23]. All mice infected
with S. aureus developed arthritis with the highest
Figure 4. Sera levels of IgG1 and IgG2a anti-bacteria and anti-parasite antibodies determined by ELISA were infected with H. polygyrus,
Nippostrongylus brasiliensis, S. aureus or Nocardia brasiliensis. Each point shows the mean (^SE) of at least 10 animals.
tissue damage including erosion of cartilage and bone
destruction that were observed in 90% of infected
mice. This aggressive arthritis may be related to the
highest IFN-g production that was found in sera of
these infected mice, our findings are in agreement with
previous publications [16]. Mice infected with other
bacteria such as Nocardia brasiliensis induced a
balanced Th1/Th2 immune response. The IL-4 levels
after infection with Nocardia brasiliensis were low in
agreement with the IFN-g production. Furthermore,
IgG1 and IgG2a anti-Nocardia brasiliensis antibodies
were increased in 42 days after infection (Figure 4). In
BALB/c experimental actinomycetoma, the host
immune response to Nocardia brasiliensis has been
reported to present both Th1 and Th2 cytokines [24].
In our study, all the infected mice with Nocardia
brasiliensis developed arthritis, however, the severity of
tissue damage was less than the S. aureus infected
group. Interestingly, in both groups of mice infected
with helminthes, less animals developed arthritis
compared with the control group, even more, in the
H. polygyrus infected group, the affected mice
presented less severity of tissue damage than observed
in the control mice. It is known that these parasites
induce a Th2 immune response and prevent the
development of excessive Th1 response [10,25]. The
balance to a Th2 response induced by parasites down
regulates several auto-immune diseases, in different
experimental animals [26]. Even more, some hel-
minthes or their antigens have been used as additional

Table II. Determination of IL-4 and IFN-g in MRL/lpr mice
infected with bacteria or parasite.
Infections agent IL-4* IFN-g
Control 223 (^77.8) 5489 (^526.8)
Nocardia brasiliensis 392 (^123.5) 6479 (^672.9)
S. aureus 357 (^85.1) 9170 (^1018.1)
H. polygyrus 495 (^50) 8000 (^645.9)
Nippostrongylus brasiliensis 500 (^88.2) 7800 (^1.5)
* The results are expressed in picograms per millilitre. Each data
point shows the mean (^SE) of at least 10 animals. Asterisk
indicates statistical differences between infected and the control
mice with p , 0.0001.
therapy in some human autoimmune disorders, such
as Crohn’s disease [27 – 29].
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Interestingly, we observed that the helminthes
species used in our study did not induce exactly the
same immune response and consequently did not
attenuate the arthritis progression at the same level.
Even though, both parasites induced a very similar Th2
response, their ability to ameliorate the tissue damage
in the joints was very different. This finding may be
related to the chronicity of parasite infection because it
is known that H. polygyrus produces a chronic infection
compared to the Nippostrongylus brasiliensis that
For personal use only.
produces an acute process [30]. Additional experi-
ments are needed to define the relationship between
the exposed time to Th2 cytokines and the severity of
arthritis.
Kidney damage has been reported in MRL/lpr
strain. In our study, control and infected mice
developed proteinuria but its degree was less severe
in MRL/lpr mice infected with helminthes (Heligmo-
somoides and Nippostrongylus) than with bacteria
(Nocardia and Staphylococcus). It has been published
that the proteinuria in MRL/lpr mice decrease after IL-
10 administration, which is a classic Th2 cytokine
[31]. We found in kidney histological examination
glomerular and tubular damage, but no significant
differences were found among control and infected
animals. However, the degree of proteinuria was lower
in the parasite-infected group. Furthermore mice
infected with S. aureus presented the highest degree of
proteinuria as compared to the other tested animals
(data not shown).
In our study, H. polygyrus and Nippostrongylus
brasiliensis clearly produced an immune modulation
that improved arthritis severity in MRL/lpr mice.
Additional experiments are necessary to clarify the
mechanisms of parasite modulation. In the future,
molecules derived from parasites will replace live
infection to prevent or control inflammatory patho-
logical responses [32,33].
In summary, our findings support the notion that a
Th2 response induced by parasite infection improved
arthritis damage and diminished the incidence of joint
tissue damage. Th1 dominant cytokines induced by
Infection affects arthritis severity 31
bacterial infection are correlated with severity of tissue
damage.
Acknowledgements
This work was supported by Grant # 47542 from
CONACYT Mexico and PAICYT, UANL, Monterrey,
México. This work fulfills part of the requirements for a
PhD degree by Guadalupe de la Cruz-Galicia. Our
thanks to Mr Reynaldo Rodriguez for technical
assistance with animals care. We are grateful to Dr
Joseph F. Urban, Jr. for kindly donating the parasites.
Our thanks go to José Angel Garza for English
corrections.
Declaration of interest: The authors report no
conflicts of interest. The authors alone are responsible
for the content and writing of the paper.
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