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The dynamics of T cells during persistent Staphylococcus aureus infection: from antigen-reactivity to in vivo anergy.

Ziegler C, Goldmann O, Hobeika E, Geffers R, Peters G, Medina E - EMBO Mol Med (2011)

Bottom Line: The mechanisms by which persistent infections are maintained involve both bacterial escape strategies and modulation of the host immune response.So far, the investigations in this area have focused on strategies used by S. aureus to persist within the host.The T cell hyporesponsiveness was reverted by co-stimulation with the phorbol ester PMA, an activator of protein kinase C, suggesting that a failure in the T cell receptor (TCR)-proximal signalling events underlie the hyporesponsive phenotype.

View Article: PubMed Central - PubMed

Affiliation: Infection Immunology Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.

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Negligible contribution of B cells to the control of S. aureus during a persistent infectionA,B. Dynamics of B cells in the spleen (A) and peripheral lymph nodes (B) of uninfected (white symbols) or S. aureus-infected C57BL/6 mice (black symbols) at progressive times after bacterial inoculation as determined by flow cytometry analysis of CD45R/B220+ cells. Each symbol represents the mean ± SD of the absolute number of B cells determined in three animals. *p < 0.05 and ***p < 0.001.C. Dot plot flow cytometry analysis of splenic B cells (CD45R/B220+) from RAG2−/− mice prior (ii) and 56 days after (iii) reconstitution with app. 107 purified B cells isolated from the spleen of C57BL/6 donor (i) mice. Dot plot analysis of splenic CD4+ and CD8+ T cells from B cells-reconstituted RAG−/− mice is shown in (iv).D. Bacterial loads in the kidneys of C57BL/6 mice (black bar) and different groups of RAG2−/− mice (white bars), non-reconstituted or reconstituted with either purified B cells or with the non-B cell fraction at 56 days after intravenous inoculation with S. aureus. Bars represent the mean ± SD of four mice per group. One representative experiment of three independent experiments is presented. ***p < 0.001.
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fig06: Negligible contribution of B cells to the control of S. aureus during a persistent infectionA,B. Dynamics of B cells in the spleen (A) and peripheral lymph nodes (B) of uninfected (white symbols) or S. aureus-infected C57BL/6 mice (black symbols) at progressive times after bacterial inoculation as determined by flow cytometry analysis of CD45R/B220+ cells. Each symbol represents the mean ± SD of the absolute number of B cells determined in three animals. *p < 0.05 and ***p < 0.001.C. Dot plot flow cytometry analysis of splenic B cells (CD45R/B220+) from RAG2−/− mice prior (ii) and 56 days after (iii) reconstitution with app. 107 purified B cells isolated from the spleen of C57BL/6 donor (i) mice. Dot plot analysis of splenic CD4+ and CD8+ T cells from B cells-reconstituted RAG−/− mice is shown in (iv).D. Bacterial loads in the kidneys of C57BL/6 mice (black bar) and different groups of RAG2−/− mice (white bars), non-reconstituted or reconstituted with either purified B cells or with the non-B cell fraction at 56 days after intravenous inoculation with S. aureus. Bars represent the mean ± SD of four mice per group. One representative experiment of three independent experiments is presented. ***p < 0.001.

Mentions: Because the above-described experiments strongly suggest that B and/or T cells are necessary for the S. aureus containment during the persistent infection, we next investigated the relevance of each population. Initially, we examined the dynamics of B cells in the spleen and peripheral lymph nodes of S. aureus-infected mice by combining cell counting and flow cytometric analysis. The total number of splenic B cells sharply increased (∼5-fold) during the first 30 days p.i. followed by a progressive decline (Fig 6A). Similarly, the number of B cells increased in the peripheral lymph nodes during the first 30 days of infection but was not statistically significant when compared with uninfected animals (Fig 6B). After day 30, the B cell population in the lymph nodes returned to values similar to uninfected controls (Fig 6B). During the course of infection, the B cells developed into plasma cells since sera from infected mice contained high titers of anti-S. aureus IgG antibodies (Fig S7 of Supporting information).


The dynamics of T cells during persistent Staphylococcus aureus infection: from antigen-reactivity to in vivo anergy.

Ziegler C, Goldmann O, Hobeika E, Geffers R, Peters G, Medina E - EMBO Mol Med (2011)

Negligible contribution of B cells to the control of S. aureus during a persistent infectionA,B. Dynamics of B cells in the spleen (A) and peripheral lymph nodes (B) of uninfected (white symbols) or S. aureus-infected C57BL/6 mice (black symbols) at progressive times after bacterial inoculation as determined by flow cytometry analysis of CD45R/B220+ cells. Each symbol represents the mean ± SD of the absolute number of B cells determined in three animals. *p < 0.05 and ***p < 0.001.C. Dot plot flow cytometry analysis of splenic B cells (CD45R/B220+) from RAG2−/− mice prior (ii) and 56 days after (iii) reconstitution with app. 107 purified B cells isolated from the spleen of C57BL/6 donor (i) mice. Dot plot analysis of splenic CD4+ and CD8+ T cells from B cells-reconstituted RAG−/− mice is shown in (iv).D. Bacterial loads in the kidneys of C57BL/6 mice (black bar) and different groups of RAG2−/− mice (white bars), non-reconstituted or reconstituted with either purified B cells or with the non-B cell fraction at 56 days after intravenous inoculation with S. aureus. Bars represent the mean ± SD of four mice per group. One representative experiment of three independent experiments is presented. ***p < 0.001.
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fig06: Negligible contribution of B cells to the control of S. aureus during a persistent infectionA,B. Dynamics of B cells in the spleen (A) and peripheral lymph nodes (B) of uninfected (white symbols) or S. aureus-infected C57BL/6 mice (black symbols) at progressive times after bacterial inoculation as determined by flow cytometry analysis of CD45R/B220+ cells. Each symbol represents the mean ± SD of the absolute number of B cells determined in three animals. *p < 0.05 and ***p < 0.001.C. Dot plot flow cytometry analysis of splenic B cells (CD45R/B220+) from RAG2−/− mice prior (ii) and 56 days after (iii) reconstitution with app. 107 purified B cells isolated from the spleen of C57BL/6 donor (i) mice. Dot plot analysis of splenic CD4+ and CD8+ T cells from B cells-reconstituted RAG−/− mice is shown in (iv).D. Bacterial loads in the kidneys of C57BL/6 mice (black bar) and different groups of RAG2−/− mice (white bars), non-reconstituted or reconstituted with either purified B cells or with the non-B cell fraction at 56 days after intravenous inoculation with S. aureus. Bars represent the mean ± SD of four mice per group. One representative experiment of three independent experiments is presented. ***p < 0.001.
Mentions: Because the above-described experiments strongly suggest that B and/or T cells are necessary for the S. aureus containment during the persistent infection, we next investigated the relevance of each population. Initially, we examined the dynamics of B cells in the spleen and peripheral lymph nodes of S. aureus-infected mice by combining cell counting and flow cytometric analysis. The total number of splenic B cells sharply increased (∼5-fold) during the first 30 days p.i. followed by a progressive decline (Fig 6A). Similarly, the number of B cells increased in the peripheral lymph nodes during the first 30 days of infection but was not statistically significant when compared with uninfected animals (Fig 6B). After day 30, the B cell population in the lymph nodes returned to values similar to uninfected controls (Fig 6B). During the course of infection, the B cells developed into plasma cells since sera from infected mice contained high titers of anti-S. aureus IgG antibodies (Fig S7 of Supporting information).

Bottom Line: The mechanisms by which persistent infections are maintained involve both bacterial escape strategies and modulation of the host immune response.So far, the investigations in this area have focused on strategies used by S. aureus to persist within the host.The T cell hyporesponsiveness was reverted by co-stimulation with the phorbol ester PMA, an activator of protein kinase C, suggesting that a failure in the T cell receptor (TCR)-proximal signalling events underlie the hyporesponsive phenotype.

View Article: PubMed Central - PubMed

Affiliation: Infection Immunology Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.

Show MeSH
Related in: MedlinePlus