Zwitterionic Polysaccharides Stimulate T Cells with No Preferential Vβ Usage and Promote Anergy, Resulting in Protection against Experimental Abscess Formation

ABSTRACT Abscesses are a classic host response to infection by many pathogenic bacteria. The immunopathogenesis of this tissue response to infection has not been fully elucidated. Previous studies have suggested that T cells are involved in the pathologic process, but the role of these cells remains unclear. To delineate the mechanism by which T cells mediate abscess formation associated with intra-abdominal sepsis, the role of T-cell activation and the contribution of antigen-presenting cells via CD28-B7 costimulation were investigated. T cells activated in vitro by zwitterionic bacterial polysaccharides (Zps) known to induce abscess formation required CD28-B7 costimulation and, when adoptively transferred to the peritoneal cavity of naı̈ve rats, promoted abscess formation. Blockade of T-cell activation via the CD28-B7 pathway in animals with CTLA4Ig prevented abscess formation following challenge with different bacterial pathogens, including Staphylococcus aureus,Bacteroides fragilis, and a combination ofEnterococcus faecium and Bacteroides distasonis. In contrast, these animals had an increased abscess rate following in vivo T-cell activation via CD28 signaling. Abscess formation in vivo and T-cell activation in vitro required costimulation by B7-2 but not B7-1. These results demonstrate that abscess formation by pathogenic bacteria is under the control of a common effector mechanism that requires T-cell activation via the CD28–B7-2 pathway.

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Role of T Lymphocytes in Liver Abscess Formation by Bacteroides fragilis in Mice

Infection and Immunity ◽

10.1128/iai.01167-10 ◽

2011 ◽

Vol 79 (6) ◽

pp. 2234-2240 ◽

Cited By ~ 1

Author(s):

Doo Ryeon Chung ◽

Hye-Rim Park ◽

Chung-Gyu Park ◽

Eung-Soo Hwang ◽

Chang-Yong Cha

Keyword(s):

T Cells ◽

T Cell ◽

Liver Abscess ◽

Bacteroides Fragilis ◽

Cell Receptor ◽

Abscess Formation ◽

Wild Type ◽

Content Type ◽

In The Wild

ABSTRACTThe underlying mechanisms of liver abscess formation have not been fully elucidated with regard to the interaction between bacterial virulence factors and the immune response. The objective of this study was to determine the role of the host T cells in liver abscess formation caused byBacteroides fragilis. We developed a liver abscess mouse model with inoculation ofB. fragilisthrough the hepatic portal vein and examined the role of T cells by studying T cell-deficient mice, as well as conducting adoptive T cell transfer experiments. No microabscess was formed in the αβ T cell receptor-positive (αβTCR+) T cell-depleted mice, in contrast to the results for the control mice. In addition, the αβTCR knockout (KO) mice showed significantly lower numbers of microabscesses, and the abscesses were smaller in size than those in the wild-type mice. Adoptive transfer of T cells purified from the wild-type mice into the αβTCR KO mice resulted in liver abscess formation in those mice. These findings suggest that T cells play an essential role in liver abscess formation caused byB. fragilisin mice.

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The Modulation of Adaptive Immune Responses by Bacterial Zwitterionic Polysaccharides

International Journal of Microbiology ◽

10.1155/2010/917075 ◽

2010 ◽

Vol 2010 ◽

pp. 1-12 ◽

Cited By ~ 10

Author(s):

Tom Li Stephen ◽

Laura Groneck ◽

Wiltrud Maria Kalka-Moll

Keyword(s):

T Cells ◽

T Cell ◽

Immune Responses ◽

Antigen Processing ◽

Adaptive Immune System ◽

Microbial Pathogens ◽

Adaptive Immune ◽

Inflammatory Conditions ◽

Adaptive Immune Cells ◽

Zwitterionic Polysaccharides

The detection of pathogen-derived molecules as foreign particles by adaptive immune cells triggers T and B lymphocytes to mount protective cellular and humoral responses, respectively. Recent immunological advances elucidated that proteins and some lipids are the principle biological molecules that induce protective T cell responses during microbial infections. Polysaccharides are important components of microbial pathogens and many vaccines. However, research concerning the activation of the adaptive immune system by polysaccharides gained interest only recently. Traditionally, polysaccharides were considered to be T cell-independent antigens that did not directly activate T cells or induce protective immune responses. Here, we review several recent advances in “carbohydrate immunobiology”. A group of bacterial polysaccharides that are known as “zwitterionic polysaccharides (ZPSs)” were recently identified as potent immune modulators. The immunomodulatory effect of ZPSs required antigen processing and presentation by antigen presenting cells, the activation of CD4 T cells and subpopulations of CD8 T cells and the modulation of host cytokine responses. In this review, we also discuss the potential use of these unique immunomodulatory ZPSs in new vaccination strategies against chronic inflammatory conditions, autoimmunity, infectious diseases, allergies and asthmatic conditions.

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