Pattern recognition receptors and control of adaptive immunity

Palm, Noah W.; Medzhitov, Ruslan

doi:10.1111/j.1600-065x.2008.00731.x

Cited by 633 publications

(526 citation statements)

References 93 publications

(185 reference statements)

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“…In particular, it remains unclear how helminth PAMPs might preferentially induce T H 2 responses that are characteristic of the immune responses to this class of pathogen. Direct skewing of adaptive responses by the mechanism of innate recognition is suggested to occur in other scenerios as well [124]. For example, C-type lectins can directly affect T H activation and differentiantion [125], thus recognition of C. albicans α-mannans by dectin-2 induces a protective T H 17-predominant response [126].…”

Section: Pathogen Recognition In Innate Immunitymentioning

confidence: 99%

NF-κB in immunobiology

2011

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NF-κB was first discovered and characterized 25 years ago as a key regulator of inducible gene expression in the immune system. Thus, it is not surprising that the clearest biological role of NF-κB is in the development and function of the immune system. Both innate and adaptive immune responses as well as the development and maintenance of the cells and tissues that comprise the immune system are, at multiple steps, under the control of the NF-κB family of transcription factors. Although this is a well-studied area of NF-κB research, new and significant findings continue to accumulate. This review will focus on these areas of recent progress while also providing a broad overview of the roles of NF-κB in mammalian immunobiology.

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Section: Pathogen Recognition In Innate Immunitymentioning

confidence: 99%

NF-κB in immunobiology

2011

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“…Many studies in mice have defined the mechanisms of PRR-mediated control of adaptive immunity orchestrated by DCs to induce effective host resistance to pathogens (see review in Ref. 17). What has not been clear is whether the amount of activation of DCs results in better T cell effector functions in settings of chronic infection in which repeated Ag stimulation, lack of CD4 help, and PD-1/PD-L1 and other inhibitory signals are believed to drive T cells to exhaustion.…”

mentioning

confidence: 99%

Dendritic Cell Inhibition Is Connected to Exhaustion of CD8+ T Cell Polyfunctionality during Chronic Hepatitis C Virus Infection

Rodrigue-Gervais

Rigsby

Jouan

et al. 2010

The Journal of Immunology

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“…DC maturation can be triggered by Toll-like receptor agonists that induce the increase in surface MHC class II and costimulatory molecules and thereby link innate to adaptive immune responses (25,26). TLR2 has already been demonstrated to be the receptor implicated in the ability of PSA to link innate and adaptive immunity (11).…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides

Gallorini

Mancuso

Cozzi

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Group B Streptococcus (GBS) causes serious infection in neonates and is an important target of vaccine development. Zwitterionic polysaccharides (ZPS), obtained through chemical introduction of positive charges into anionic polysaccharides (PS) from GBS, have the ability to activate human and mouse antigen presenting cells (APCs) through toll-like receptor 2 (TLR2).To generate a polysaccharide vaccine with antigen (Ag) and adjuvant properties in one molecule, we have conjugated ZPS with a carrier protein. ZPS-glycoconjugates induce higher T-cell and Ab responses to carrier and PS, respectively, compared to control PS-glycoconjugates made with the native polysaccharide form. The increased immunogenicity of ZPS-conjugates correlates with their ability to activate dendritic cells (DCs). Moreover, protection of mothers or neonate offspring from lethal GBS challenge is better when mothers are immunized with ZPS-conjugates compared to immunization with PS-conjugates. In TLR2 knockout mice, ZPS-conjugates lose both their increased immunogenicity and protective effect after vaccination. When ZPS are coadministered as adjuvants with unconjugated tetanus toxoid (TT), they have the ability to increase the TT-specific antibody titer. In conclusion, glycoconjugates containing ZPS are potent vaccines. They target Ag to TLR2-expressing APCs and activate these APCs, leading to better T-cell priming and ultimately to higher protective Ab titers. Thus, rational chemical design can generate potent PS-adjuvants with wide application, including glycoconjugates and coadministration with unrelated protein Ags.adjuvant ͉ dendritic cell ͉ Group B Streptococcus C lassically, capsular polysaccharides (PS) from bacteria are considered to be T-independent Ags (1) able to activate B cells directly, without a contribution of help by CD4 ϩ T cells. Therefore, the immune response to PS fails to induce significant and prolonged titers of antibody with high avidity in infants and persistent Agspecific memory B cells in adults. For this reason, in vaccines, PS are mostly used conjugated with a carrier protein that provides T-cell help and consequently immunological memory (2). Glycoconjugate vaccines against the Gram-positive bacterium Group B Streptococcus (GBS) have been shown to confer serotype specific protection in mice and have been tested in clinical trials (3). In humans, addition of alum to the vaccine formulation did not further increase the immune response induced (4). In contrast, in animal models, adsorption to Al(OH) 3 (alum) enhances the immunogenicity of the glycoconjugate (5, 6) which may be explained by the possibility that animals are more naive to GBS than humans. Moreover, a number of commercially available glycoconjugate vaccines, such as those against Meningococcus C, Haemophilus influenza, and the 7-valent Pneumococcus vaccine, use alum or aluminium phosphate as an adjuvant. Thus, the combination of glycoconjugates with adjuvants likely generates potent vaccines, able to activate APCs and induce strong Ag-specific T and B c...

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Pattern recognition receptors and control of adaptive immunity

Cited by 633 publications

References 93 publications

NF-κB in immunobiology

NF-κB in immunobiology

Dendritic Cell Inhibition Is Connected to Exhaustion of CD8+ T Cell Polyfunctionality during Chronic Hepatitis C Virus Infection

Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides

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