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Altered distribution of peripheral blood memory B cells in humans chronically infected with Trypanosoma cruzi.

Fernández ER, Olivera GC, Quebrada Palacio LP, González MN, Hernandez-Vasquez Y, Sirena NM, Morán ML, Ledesma Patiño OS, Postan M - PLoS ONE (2014)

Bottom Line: Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells.Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas.In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Investigación, Instituto Nacional de Parasitología "Dr. Mario Fatala Chabén", Ciudad Autónoma de Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.

ABSTRACT
Numerous abnormalities of the peripheral blood T cell compartment have been reported in human chronic Trypanosoma cruzi infection and related to prolonged antigenic stimulation by persisting parasites. Herein, we measured circulating lymphocytes of various phenotypes based on the differential expression of CD19, CD4, CD27, CD10, IgD, IgM, IgG and CD138 in a total of 48 T. cruzi-infected individuals and 24 healthy controls. Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells. The contraction of CD19+CD27+ cells was comprised of IgG+IgD-, IgM+IgD- and isotype switched IgM-IgD- memory B cells, CD19+CD10+CD27+ B cell precursors and terminally differentiated CD19+CD27+CD138+ plasma cells. Conversely, infected individuals had increased proportions of CD19+IgG+CD27-IgD- memory and CD19+IgM+CD27-IgD+ transitional/naïve B cells. These observations prompted us to assess soluble CD27, a molecule generated by the cleavage of membrane-bound CD27 and used to monitor systemic immune activation. Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas. In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans.

No MeSH data available.


Related in: MedlinePlus

Distribution of the major circulating B cell subsets in individuals chronically infected with Trypanosoma cruzi.(A) Representative samples from a healthy control donor and a T. cruzi-infected individual. PBMC were stained with Abs to CD19, CD27, IgD, CD10 and CD138 and analyzed by flow cytometry. Plots show a typical staining for CD19+ cells (histogram) and major B cell subsets among gated CD19+ cells. Numbers represent the percentage of cells within the gate. (B) Box and whiskers (min to max) show the percentage of cells expressing the indicated markers. Mann-Whitney nonparametric test or U-test was used for statistical significance (p values).
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pone-0104951-g001: Distribution of the major circulating B cell subsets in individuals chronically infected with Trypanosoma cruzi.(A) Representative samples from a healthy control donor and a T. cruzi-infected individual. PBMC were stained with Abs to CD19, CD27, IgD, CD10 and CD138 and analyzed by flow cytometry. Plots show a typical staining for CD19+ cells (histogram) and major B cell subsets among gated CD19+ cells. Numbers represent the percentage of cells within the gate. (B) Box and whiskers (min to max) show the percentage of cells expressing the indicated markers. Mann-Whitney nonparametric test or U-test was used for statistical significance (p values).

Mentions: In order to evaluate whether T. cruzi infection affects the phenotype of the PB B cell pool in humans, we first determined the overall proportion of B cells by staining PBMC from 48 T. cruzi-infected individuals and 24 uninfected controls with anti-CD19 (Fig. 1A). The proportion of CD19+ cells in infected individuals was significantly lower compared to controls (mean percentage ± SD = 12.53±6.37 and 16.86±7.48, respectively; P = 0.0177). However, absolute numbers of CD19+ cells, estimated for a subset of infected individuals, were found comparable to that observed in controls (Table 1). We then evaluated the major circulating B cell subsets based on the differential expression of CD27 and IgD on CD19+ cells (Fig. 1A). T. cruzi-infected individuals had significantly lower frequencies of CD27+IgD- and CD27+IgD+ B cells, and higher frequencies of CD27-IgD+ B cells compared to controls (p<0.05); the levels of CD27-IgD- B cells in infected individuals were comparable to that in controls (Fig. 1B).


Altered distribution of peripheral blood memory B cells in humans chronically infected with Trypanosoma cruzi.

Fernández ER, Olivera GC, Quebrada Palacio LP, González MN, Hernandez-Vasquez Y, Sirena NM, Morán ML, Ledesma Patiño OS, Postan M - PLoS ONE (2014)

Distribution of the major circulating B cell subsets in individuals chronically infected with Trypanosoma cruzi.(A) Representative samples from a healthy control donor and a T. cruzi-infected individual. PBMC were stained with Abs to CD19, CD27, IgD, CD10 and CD138 and analyzed by flow cytometry. Plots show a typical staining for CD19+ cells (histogram) and major B cell subsets among gated CD19+ cells. Numbers represent the percentage of cells within the gate. (B) Box and whiskers (min to max) show the percentage of cells expressing the indicated markers. Mann-Whitney nonparametric test or U-test was used for statistical significance (p values).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128741&req=5

pone-0104951-g001: Distribution of the major circulating B cell subsets in individuals chronically infected with Trypanosoma cruzi.(A) Representative samples from a healthy control donor and a T. cruzi-infected individual. PBMC were stained with Abs to CD19, CD27, IgD, CD10 and CD138 and analyzed by flow cytometry. Plots show a typical staining for CD19+ cells (histogram) and major B cell subsets among gated CD19+ cells. Numbers represent the percentage of cells within the gate. (B) Box and whiskers (min to max) show the percentage of cells expressing the indicated markers. Mann-Whitney nonparametric test or U-test was used for statistical significance (p values).
Mentions: In order to evaluate whether T. cruzi infection affects the phenotype of the PB B cell pool in humans, we first determined the overall proportion of B cells by staining PBMC from 48 T. cruzi-infected individuals and 24 uninfected controls with anti-CD19 (Fig. 1A). The proportion of CD19+ cells in infected individuals was significantly lower compared to controls (mean percentage ± SD = 12.53±6.37 and 16.86±7.48, respectively; P = 0.0177). However, absolute numbers of CD19+ cells, estimated for a subset of infected individuals, were found comparable to that observed in controls (Table 1). We then evaluated the major circulating B cell subsets based on the differential expression of CD27 and IgD on CD19+ cells (Fig. 1A). T. cruzi-infected individuals had significantly lower frequencies of CD27+IgD- and CD27+IgD+ B cells, and higher frequencies of CD27-IgD+ B cells compared to controls (p<0.05); the levels of CD27-IgD- B cells in infected individuals were comparable to that in controls (Fig. 1B).

Bottom Line: Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells.Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas.In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Investigación, Instituto Nacional de Parasitología "Dr. Mario Fatala Chabén", Ciudad Autónoma de Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.

ABSTRACT
Numerous abnormalities of the peripheral blood T cell compartment have been reported in human chronic Trypanosoma cruzi infection and related to prolonged antigenic stimulation by persisting parasites. Herein, we measured circulating lymphocytes of various phenotypes based on the differential expression of CD19, CD4, CD27, CD10, IgD, IgM, IgG and CD138 in a total of 48 T. cruzi-infected individuals and 24 healthy controls. Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells. The contraction of CD19+CD27+ cells was comprised of IgG+IgD-, IgM+IgD- and isotype switched IgM-IgD- memory B cells, CD19+CD10+CD27+ B cell precursors and terminally differentiated CD19+CD27+CD138+ plasma cells. Conversely, infected individuals had increased proportions of CD19+IgG+CD27-IgD- memory and CD19+IgM+CD27-IgD+ transitional/naïve B cells. These observations prompted us to assess soluble CD27, a molecule generated by the cleavage of membrane-bound CD27 and used to monitor systemic immune activation. Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas. In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans.

No MeSH data available.


Related in: MedlinePlus