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The "sweet" side of a long pentraxin: how glycosylation affects PTX3 functions in innate immunity and inflammation.

Inforzato A, Reading PC, Barbati E, Bottazzi B, Garlanda C, Mantovani A - Front Immunol (2013)

Bottom Line: Glycosylation has been implicated in a number of PTX3 activities, including neutralization of influenza viruses, modulation of the complement system, and attenuation of leukocyte recruitment.Therefore, this post translational modification might act as a fine tuner of PTX3 functions in native immunity and inflammation.Here we review the studies on PTX3, with emphasis on the glycan-dependent mechanisms underlying pathogen recognition and crosstalk with other components of the innate immune system.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Inflammation, Humanitas Clinical and Research Center Rozzano, Italy.

ABSTRACT
Innate immunity represents the first line of defense against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognize pathogen-associated molecular patterns and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a non-redundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the crossroad between innate immunity, inflammation, and female fertility. The human PTX3 protein contains a single N-glycosylation site that is fully occupied by complex type oligosaccharides, mainly fucosylated and sialylated biantennary glycans. Glycosylation has been implicated in a number of PTX3 activities, including neutralization of influenza viruses, modulation of the complement system, and attenuation of leukocyte recruitment. Therefore, this post translational modification might act as a fine tuner of PTX3 functions in native immunity and inflammation. Here we review the studies on PTX3, with emphasis on the glycan-dependent mechanisms underlying pathogen recognition and crosstalk with other components of the innate immune system.

No MeSH data available.


Related in: MedlinePlus

Glycosylation as a tuner of PTX3 functions in innate immunity. A number of both somatic and immune cell types produce PTX3 at sites of infection/inflammation. The glycosylation status of PTX3 (e.g., branching and sialylation) might change depending on cellular source and inducing stimuli (a). In addition, the protein oligosaccharides might undergo processing by glycosidases, including neuraminidase, which are expressed or mobilized on the surface of both pathogens and host cells (e.g., neutrophils) (b). Desialylated PTX3 has higher affinity for C1q but loses recognition of ficolin-1 and influenza virus (c).
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Figure 2: Glycosylation as a tuner of PTX3 functions in innate immunity. A number of both somatic and immune cell types produce PTX3 at sites of infection/inflammation. The glycosylation status of PTX3 (e.g., branching and sialylation) might change depending on cellular source and inducing stimuli (a). In addition, the protein oligosaccharides might undergo processing by glycosidases, including neuraminidase, which are expressed or mobilized on the surface of both pathogens and host cells (e.g., neutrophils) (b). Desialylated PTX3 has higher affinity for C1q but loses recognition of ficolin-1 and influenza virus (c).

Mentions: Interestingly, we have reported that the glycosylation status of PTX3 modulates the protein interaction with C1q mostly through the terminal residues of sialic acid. In fact, either desialylation or complete deglycosylation of the long pentraxin equally increase its binding to C1q (Inforzato et al., 2006). Consistent with this, hydrolysis of the terminal residues of sialic acid enhances the PTX3-dependent activation of the classical pathway of complement, as assessed by C3 and C4 deposition on PTX3-coated surfaces. Furthermore, in the fluid phase desialylated PTX3 is a stronger inhibitor of the C1q hemolytic activity than the fully glycosylated protein. Therefore the strengthening of PTX3 binding to C1q that occurs upon removal of sialic acid is independent of the way the long pentraxin is presented (i.e., either immobilized or in solution). Also, sialylation of the PTX3 oligosaccharides might provide a strategy to fine tune both the activating and inhibitory activities of this long pentraxin on the classical complement cascade (Figure 2).


The "sweet" side of a long pentraxin: how glycosylation affects PTX3 functions in innate immunity and inflammation.

Inforzato A, Reading PC, Barbati E, Bottazzi B, Garlanda C, Mantovani A - Front Immunol (2013)

Glycosylation as a tuner of PTX3 functions in innate immunity. A number of both somatic and immune cell types produce PTX3 at sites of infection/inflammation. The glycosylation status of PTX3 (e.g., branching and sialylation) might change depending on cellular source and inducing stimuli (a). In addition, the protein oligosaccharides might undergo processing by glycosidases, including neuraminidase, which are expressed or mobilized on the surface of both pathogens and host cells (e.g., neutrophils) (b). Desialylated PTX3 has higher affinity for C1q but loses recognition of ficolin-1 and influenza virus (c).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539679&req=5

Figure 2: Glycosylation as a tuner of PTX3 functions in innate immunity. A number of both somatic and immune cell types produce PTX3 at sites of infection/inflammation. The glycosylation status of PTX3 (e.g., branching and sialylation) might change depending on cellular source and inducing stimuli (a). In addition, the protein oligosaccharides might undergo processing by glycosidases, including neuraminidase, which are expressed or mobilized on the surface of both pathogens and host cells (e.g., neutrophils) (b). Desialylated PTX3 has higher affinity for C1q but loses recognition of ficolin-1 and influenza virus (c).
Mentions: Interestingly, we have reported that the glycosylation status of PTX3 modulates the protein interaction with C1q mostly through the terminal residues of sialic acid. In fact, either desialylation or complete deglycosylation of the long pentraxin equally increase its binding to C1q (Inforzato et al., 2006). Consistent with this, hydrolysis of the terminal residues of sialic acid enhances the PTX3-dependent activation of the classical pathway of complement, as assessed by C3 and C4 deposition on PTX3-coated surfaces. Furthermore, in the fluid phase desialylated PTX3 is a stronger inhibitor of the C1q hemolytic activity than the fully glycosylated protein. Therefore the strengthening of PTX3 binding to C1q that occurs upon removal of sialic acid is independent of the way the long pentraxin is presented (i.e., either immobilized or in solution). Also, sialylation of the PTX3 oligosaccharides might provide a strategy to fine tune both the activating and inhibitory activities of this long pentraxin on the classical complement cascade (Figure 2).

Bottom Line: Glycosylation has been implicated in a number of PTX3 activities, including neutralization of influenza viruses, modulation of the complement system, and attenuation of leukocyte recruitment.Therefore, this post translational modification might act as a fine tuner of PTX3 functions in native immunity and inflammation.Here we review the studies on PTX3, with emphasis on the glycan-dependent mechanisms underlying pathogen recognition and crosstalk with other components of the innate immune system.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Inflammation, Humanitas Clinical and Research Center Rozzano, Italy.

ABSTRACT
Innate immunity represents the first line of defense against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognize pathogen-associated molecular patterns and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a non-redundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the crossroad between innate immunity, inflammation, and female fertility. The human PTX3 protein contains a single N-glycosylation site that is fully occupied by complex type oligosaccharides, mainly fucosylated and sialylated biantennary glycans. Glycosylation has been implicated in a number of PTX3 activities, including neutralization of influenza viruses, modulation of the complement system, and attenuation of leukocyte recruitment. Therefore, this post translational modification might act as a fine tuner of PTX3 functions in native immunity and inflammation. Here we review the studies on PTX3, with emphasis on the glycan-dependent mechanisms underlying pathogen recognition and crosstalk with other components of the innate immune system.

No MeSH data available.


Related in: MedlinePlus