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BAFF mediates splenic B cell response and antibody production in experimental Chagas disease.

Bermejo DA, Amezcua-Vesely MC, Montes CL, Merino MC, Gehrau RC, Cejas H, Acosta-Rodríguez EV, Gruppi A - PLoS Negl Trop Dis (2010)

Bottom Line: Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia, delayed specific humoral immunity and high levels of non-parasite specific antibodies.Interestingly, BAFF inhibition favors the parasitism in heart.Our results demonstrate, for the first time, an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, School of Chemical Sciences, National University of Córdoba, Córdoba, Argentina.

ABSTRACT

Background: B cells and antibodies are involved not only in controlling the spread of blood circulating Trypanosoma cruzi, but also in the autoreactive manifestations observed in Chagas disease. Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia, delayed specific humoral immunity and high levels of non-parasite specific antibodies. Since TNF superfamily B lymphocyte Stimulator (BAFF) mediates polyclonal B cell response in vitro triggered by T. cruzi antigens, and BAFF-Tg mice show similar signs to T. cruzi infected mice, we hypothesized that BAFF can mediate polyclonal B cell response in experimental Chagas disease.

Methodology/principal findings: BAFF is produced early and persists throughout the infection. To analyze BAFF role in experimental Chagas disease, Balb/c infected mice were injected with BR3:Fc, a soluble receptor of BAFF, to block BAFF activity. By BAFF blockade we observed that this cytokine mediates the mature B cell response and the production of non-parasite specific IgM and IgG. BAFF also influences the development of antinuclear IgG and parasite-specific IgM response, not affecting T. cruzi-specific IgG and parasitemia. Interestingly, BAFF inhibition favors the parasitism in heart.

Conclusions/significance: Our results demonstrate, for the first time, an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.

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Circulating and tissue parasites in T. cruzi infected mice treated with BR3:Fc.A, Number of circulating parasites in blood samples from T. cruzi infected mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) or IgG2a control (I+IgG2a) was determined at days 15 p.i. by counting in Neubauer chamber. B, Photomicrographs from heart sections obtained from T. cruzi infected mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) stained with hematoxilina/eosina (400X). Amastigote nests are demarcated with squares. Inset shows one of them (1000X). C, Number of amastigote nests counted in 100 histological fields of hearts. Diamonds represent the value obtained from each mouse. The lines represent the media value in each day p.i. Results are representative for two individual experiments.
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pntd-0000679-g007: Circulating and tissue parasites in T. cruzi infected mice treated with BR3:Fc.A, Number of circulating parasites in blood samples from T. cruzi infected mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) or IgG2a control (I+IgG2a) was determined at days 15 p.i. by counting in Neubauer chamber. B, Photomicrographs from heart sections obtained from T. cruzi infected mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) stained with hematoxilina/eosina (400X). Amastigote nests are demarcated with squares. Inset shows one of them (1000X). C, Number of amastigote nests counted in 100 histological fields of hearts. Diamonds represent the value obtained from each mouse. The lines represent the media value in each day p.i. Results are representative for two individual experiments.

Mentions: To analyze if B cell reduction and the decrease of IgM parasite-specific Abs affected the parasite replication, we measured the number of circulating trypomastigotes in blood of infected mice and the grade of tissue parasitism by evaluating amastigote niches in heart. Parasitemia was similar in T. cruzi infected mice treated with physiological solution, BR3:Fc or IgG2a control (Fig 7A), while cardiac parasitism was increased in BR3:Fc treated infected mice in comparison to untreated infected mice (Fig 7B,C). Thus, the hearts of infected mice in which BAFF activity was blocked had higher number of nest of amastigotes in the myocardial fibers of the auricle than non-treated infected mice (Fig 7B,C).


BAFF mediates splenic B cell response and antibody production in experimental Chagas disease.

Bermejo DA, Amezcua-Vesely MC, Montes CL, Merino MC, Gehrau RC, Cejas H, Acosta-Rodríguez EV, Gruppi A - PLoS Negl Trop Dis (2010)

Circulating and tissue parasites in T. cruzi infected mice treated with BR3:Fc.A, Number of circulating parasites in blood samples from T. cruzi infected mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) or IgG2a control (I+IgG2a) was determined at days 15 p.i. by counting in Neubauer chamber. B, Photomicrographs from heart sections obtained from T. cruzi infected mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) stained with hematoxilina/eosina (400X). Amastigote nests are demarcated with squares. Inset shows one of them (1000X). C, Number of amastigote nests counted in 100 histological fields of hearts. Diamonds represent the value obtained from each mouse. The lines represent the media value in each day p.i. Results are representative for two individual experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2864296&req=5

pntd-0000679-g007: Circulating and tissue parasites in T. cruzi infected mice treated with BR3:Fc.A, Number of circulating parasites in blood samples from T. cruzi infected mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) or IgG2a control (I+IgG2a) was determined at days 15 p.i. by counting in Neubauer chamber. B, Photomicrographs from heart sections obtained from T. cruzi infected mice treated with physiological solution (I) or BR3:Fc (I+BR3:Fc) stained with hematoxilina/eosina (400X). Amastigote nests are demarcated with squares. Inset shows one of them (1000X). C, Number of amastigote nests counted in 100 histological fields of hearts. Diamonds represent the value obtained from each mouse. The lines represent the media value in each day p.i. Results are representative for two individual experiments.
Mentions: To analyze if B cell reduction and the decrease of IgM parasite-specific Abs affected the parasite replication, we measured the number of circulating trypomastigotes in blood of infected mice and the grade of tissue parasitism by evaluating amastigote niches in heart. Parasitemia was similar in T. cruzi infected mice treated with physiological solution, BR3:Fc or IgG2a control (Fig 7A), while cardiac parasitism was increased in BR3:Fc treated infected mice in comparison to untreated infected mice (Fig 7B,C). Thus, the hearts of infected mice in which BAFF activity was blocked had higher number of nest of amastigotes in the myocardial fibers of the auricle than non-treated infected mice (Fig 7B,C).

Bottom Line: Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia, delayed specific humoral immunity and high levels of non-parasite specific antibodies.Interestingly, BAFF inhibition favors the parasitism in heart.Our results demonstrate, for the first time, an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, School of Chemical Sciences, National University of Córdoba, Córdoba, Argentina.

ABSTRACT

Background: B cells and antibodies are involved not only in controlling the spread of blood circulating Trypanosoma cruzi, but also in the autoreactive manifestations observed in Chagas disease. Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia, delayed specific humoral immunity and high levels of non-parasite specific antibodies. Since TNF superfamily B lymphocyte Stimulator (BAFF) mediates polyclonal B cell response in vitro triggered by T. cruzi antigens, and BAFF-Tg mice show similar signs to T. cruzi infected mice, we hypothesized that BAFF can mediate polyclonal B cell response in experimental Chagas disease.

Methodology/principal findings: BAFF is produced early and persists throughout the infection. To analyze BAFF role in experimental Chagas disease, Balb/c infected mice were injected with BR3:Fc, a soluble receptor of BAFF, to block BAFF activity. By BAFF blockade we observed that this cytokine mediates the mature B cell response and the production of non-parasite specific IgM and IgG. BAFF also influences the development of antinuclear IgG and parasite-specific IgM response, not affecting T. cruzi-specific IgG and parasitemia. Interestingly, BAFF inhibition favors the parasitism in heart.

Conclusions/significance: Our results demonstrate, for the first time, an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.

Show MeSH
Related in: MedlinePlus