Streptococcus pneumoniae Serotype 1 Capsular Polysaccharide Induces CD8+CD28− Regulatory T Lymphocytes by TCR Crosslinking

Mertens, Jane; Fabri, Mario; Zingarelli, Alessandra; Kubacki, Torsten; Meemboor, Sonja; Groneck, Laura; Seeger, Jens M.; Bessler, Martina; Hafke, Helena; Odenthal, Margarete; Bieler, Joan Glick; Schneck, Jonathan P.; Kashkar, Hamid

doi:10.1371/journal.ppat.1000596

Cited by 20 publications

(23 citation statements)

References 80 publications

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“…A very different mechanism is employed by Streptococcus pneumoniae which elaborates a zwitterionic polysaccharide able to directly cross-link the TCR of CD8 þ T cells and switch them into a regulatory phenotype (Mertens et al, 2009). As with the H. polygyrus HES, this is a process which can by-pass any requirement for an APC population.…”

Section: Direct Conversion Of T Cells Into Tregsmentioning

confidence: 99%

Regulatory T Cells in Infection

Maizels

Smith

2011

Advances in Immunology

106

109

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Infectious agents have intimately co-evolved with the host immune system, acquiring a portfolio of highly sophisticated mechanisms to modulate immunity. Among the common strategies developed by viruses, bacteria, protozoa, helminths, and fungi is the manipulation of the regulatory T cell network in order to favor pathogen survival and transmission. Treg activity also benefits the host in many circumstances by controlling immunopathogenic reactions to infection. Interestingly, some pathogens are able to directly induce the conversion of naive T cells into suppressive Foxp3-expressing Tregs, while others activate pre-existing natural Tregs, in both cases repressing pathogen-specific effector responses. However, Tregs can also act to promote immunity in certain settings, such as in initial stages of infection when effector cells must access the site of infection, and subsequently in ensuring generation of effector memory. Notably, there is little current information on whether infections selectively drive pathogen-specific Tregs, and if so whether these cells are also reactive to self-antigens. Further analysis of specificity, together with a clearer picture of the relative dynamics of Treg subsets over the course of disease, should lead to rational strategies for immune intervention to optimize immunity and eliminate infection.

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Section: Direct Conversion Of T Cells Into Tregsmentioning

confidence: 99%

Regulatory T Cells in Infection

Maizels

Smith

2011

Advances in Immunology

106

109

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“…Intraperitoneal administration of S. pneumoniae serotype 1 capsular polysaccharide induces CD8 + CD28 − T-cells with a regulatory phenotype [18] that synthesize both IL-10 and TGF-β and are immunosuppressive for CD4 + T cells in vivo and in vitro . However, whether regulatory cells play protective roles during infection with invasive S. pneumoniae strains remained to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

T Regulatory Cells Control Susceptibility to Invasive Pneumococcal Pneumonia in Mice

et al. 2012

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Streptococcus pneumoniae is an important human pathogen responsible for a spectrum of diseases including pneumonia. Immunological and pro-inflammatory processes induced in the lung during pneumococcal infection are well documented, but little is known about the role played by immunoregulatory cells and cytokines in the control of such responses. We demonstrate considerable differences in the immunomodulatory cytokine transforming growth factor (TGF)-β between the pneumococcal pneumonia resistant BALB/c and susceptible CBA/Ca mouse strains. Immunohistochemistry and flow cytometry reveal higher levels of TGF-β protein in BALB/c lungs during pneumococcal pneumonia that correlates with a rapid rise in lung Foxp3+Helios+ T regulatory cells. These cells have protective functions during pneumococcal pneumonia, because blocking their induction with an inhibitor of TGF-β impairs BALB/c resistance to infection and aids bacterial dissemination from lungs. Conversely, adoptive transfer of T regulatory cells to CBA/Ca mice, prior to infection, prolongs survival and decreases bacterial dissemination from lungs to blood. Importantly, strong T regulatory cell responses also correlate with disease-resistance in outbred MF1 mice, confirming the importance of immunoregulatory cells in controlling protective responses to the pneumococcus. This study provides exciting new evidence for the importance of immunomodulation during pulmonary pneumococcal infection and suggests that TGF-β signalling is a potential target for immunotherapy or drug design.

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“…Accordingly, PSA is unable to protect TLR2 −/− animals from experimental colitis (37). The ZPS Sp1 was found to induce immunosuppressive, IL‐10‐producing CD8 + CD28 − T cells (98), which prevent colitis in the CD4 + CD45Rb transfer model (99). This finding raises the possibility that ZPS molecules may possess multiple mechanisms for stimulating anti‐inflammatory responses.…”

Section: The Yang: Bacterial Polysaccharides As Immunoregulatory Agentsmentioning

confidence: 99%

The yin yang of bacterial polysaccharides: lessons learned from B. fragilis PSA

Surana

Kasper

2011

Immunological Reviews

136

123

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Summary Over the past several years, there have been remarkable advances in our understanding of how commensal organisms shape host immunity. Although the full cast of immunogenic bacteria and their immunomodulatory molecules remains to be elucidated, lessons learned from the interactions between bacterial zwitterionic polysaccharides (ZPSs) and the host immune system represent an integral step toward better understanding how the intestinal microbiota effect immunologic changes. Somewhat paradoxically, ZPSs, which are found in numerous commensal organisms, are able to elicit both proinflammatory and immunoregulatory responses; both of these outcomes involve fine-tuning the balance between T-helper 17 cells and interleukin-10–producing regulatory T cells. In this review, we discuss the immunomodulatory effects of the archetypal ZPS, Bacteroides fragilis PSA. In addition, we highlight some of the opportunities and challenges in applying these lessons in clinical settings.

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Streptococcus pneumoniae Serotype 1 Capsular Polysaccharide Induces CD8+CD28− Regulatory T Lymphocytes by TCR Crosslinking

Cited by 20 publications

References 80 publications

Regulatory T Cells in Infection

Regulatory T Cells in Infection

T Regulatory Cells Control Susceptibility to Invasive Pneumococcal Pneumonia in Mice

The yin yang of bacterial polysaccharides: lessons learned from B. fragilis PSA

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