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Recognition of Neisseria meningitidis by the long pentraxin PTX3 and its role as an endogenous adjuvant.

Bottazzi B, Santini L, Savino S, Giuliani MM, Dueñas Díez AI, Mancuso G, Beninati C, Sironi M, Valentino S, Deban L, Garlanda C, Teti G, Pizza M, Rappuoli R, Mantovani A - PLoS ONE (2015)

Bottom Line: PTX3-recognized microbial moieties are conserved structures which fulfil essential microbial functions.Administration of PTX3 reduced the bacterial load in infant rats challenged with Neisseria meningitidis.These results suggest that PTX3 recognizes a set of conserved structures from Neisseria meningitidis and acts as an amplifier/endogenous adjuvant of responses to this bacterium.

View Article: PubMed Central - PubMed

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

ABSTRACT
Long pentraxin 3 (PTX3) is a non-redundant component of the humoral arm of innate immunity. The present study was designed to investigate the interaction of PTX3 with Neisseria meningitidis. PTX3 bound acapsular meningococcus, Neisseria-derived outer membrane vesicles (OMV) and 3 selected meningococcal antigens (GNA0667, GNA1030 and GNA2091). PTX3-recognized microbial moieties are conserved structures which fulfil essential microbial functions. Ptx3-deficient mice had a lower antibody response in vaccination protocols with OMV and co-administration of PTX3 increased the antibody response, particularly in Ptx3-deficient mice. Administration of PTX3 reduced the bacterial load in infant rats challenged with Neisseria meningitidis. These results suggest that PTX3 recognizes a set of conserved structures from Neisseria meningitidis and acts as an amplifier/endogenous adjuvant of responses to this bacterium.

No MeSH data available.


Related in: MedlinePlus

Bactericidal activity of serum from mice immunized with OMV.WT and ptx3-/- mice were immunized by ip or im treatment with OMV and sera were collected two weeks after the last immunization. Data are presented as mean SBA titres ± SD a) comparison of log SBA titres in WT and ptx3-/- mice (** p<0.01, paired Student’s t test; pooled data from ip immunized animals). b) mean SBA titres in representative experiments performed in WT and ptx3-/- mice immunized ip (WT n = 8 ptx3-/- n = 6) or im (WT n = 15, ptx3-/- n = 16) with 0.05 (ip) or 0.5 (im) μg OMV. c) mean SBA titres in WT and ptx3-/- mice immunized with 0.05 μg OMV ± 2 μg PTX3 [one out of three experiments; WT(OMV), n = 8; WT(OMV+PTX3), n = 7; ptx3-/-(OMV), n = 6; ptx3-/-(OMV+PTX3), n = 8]. *p<0.5; ** p<0.01 (Student’s t test).
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pone.0120807.g005: Bactericidal activity of serum from mice immunized with OMV.WT and ptx3-/- mice were immunized by ip or im treatment with OMV and sera were collected two weeks after the last immunization. Data are presented as mean SBA titres ± SD a) comparison of log SBA titres in WT and ptx3-/- mice (** p<0.01, paired Student’s t test; pooled data from ip immunized animals). b) mean SBA titres in representative experiments performed in WT and ptx3-/- mice immunized ip (WT n = 8 ptx3-/- n = 6) or im (WT n = 15, ptx3-/- n = 16) with 0.05 (ip) or 0.5 (im) μg OMV. c) mean SBA titres in WT and ptx3-/- mice immunized with 0.05 μg OMV ± 2 μg PTX3 [one out of three experiments; WT(OMV), n = 8; WT(OMV+PTX3), n = 7; ptx3-/-(OMV), n = 6; ptx3-/-(OMV+PTX3), n = 8]. *p<0.5; ** p<0.01 (Student’s t test).

Mentions: PTX3 is one of the genes rapidly induced following treatment with adjuvants such as MF59 and CpG [57], raising the possibility that this molecule may behave as an endogenous adjuvant. To investigate this possibility we compared the response of WT and ptx3-/- animals in immunization protocols with OMV. Animals were immunized with OMV (0.5–0.05 μg/ml) by ip or im injection, and serum was collected two weeks after the last immunization. Seven experiments were performed with 7–20 mice per group over a period of three years (Table 1). Fig. 5a shows the pooled data from experiments 1 to 5 (ip immunization) and Fig. 5b reports two representative experiments, one for each immunization route (experiments 6 and 7). Although there was considerable variability in serum bactericidal antibody (SBA) titers within experimental groups and from experiment to experiment, ptx3-deficiency was associated with a significant reduction in antibody production.


Recognition of Neisseria meningitidis by the long pentraxin PTX3 and its role as an endogenous adjuvant.

Bottazzi B, Santini L, Savino S, Giuliani MM, Dueñas Díez AI, Mancuso G, Beninati C, Sironi M, Valentino S, Deban L, Garlanda C, Teti G, Pizza M, Rappuoli R, Mantovani A - PLoS ONE (2015)

Bactericidal activity of serum from mice immunized with OMV.WT and ptx3-/- mice were immunized by ip or im treatment with OMV and sera were collected two weeks after the last immunization. Data are presented as mean SBA titres ± SD a) comparison of log SBA titres in WT and ptx3-/- mice (** p<0.01, paired Student’s t test; pooled data from ip immunized animals). b) mean SBA titres in representative experiments performed in WT and ptx3-/- mice immunized ip (WT n = 8 ptx3-/- n = 6) or im (WT n = 15, ptx3-/- n = 16) with 0.05 (ip) or 0.5 (im) μg OMV. c) mean SBA titres in WT and ptx3-/- mice immunized with 0.05 μg OMV ± 2 μg PTX3 [one out of three experiments; WT(OMV), n = 8; WT(OMV+PTX3), n = 7; ptx3-/-(OMV), n = 6; ptx3-/-(OMV+PTX3), n = 8]. *p<0.5; ** p<0.01 (Student’s t test).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4364741&req=5

pone.0120807.g005: Bactericidal activity of serum from mice immunized with OMV.WT and ptx3-/- mice were immunized by ip or im treatment with OMV and sera were collected two weeks after the last immunization. Data are presented as mean SBA titres ± SD a) comparison of log SBA titres in WT and ptx3-/- mice (** p<0.01, paired Student’s t test; pooled data from ip immunized animals). b) mean SBA titres in representative experiments performed in WT and ptx3-/- mice immunized ip (WT n = 8 ptx3-/- n = 6) or im (WT n = 15, ptx3-/- n = 16) with 0.05 (ip) or 0.5 (im) μg OMV. c) mean SBA titres in WT and ptx3-/- mice immunized with 0.05 μg OMV ± 2 μg PTX3 [one out of three experiments; WT(OMV), n = 8; WT(OMV+PTX3), n = 7; ptx3-/-(OMV), n = 6; ptx3-/-(OMV+PTX3), n = 8]. *p<0.5; ** p<0.01 (Student’s t test).
Mentions: PTX3 is one of the genes rapidly induced following treatment with adjuvants such as MF59 and CpG [57], raising the possibility that this molecule may behave as an endogenous adjuvant. To investigate this possibility we compared the response of WT and ptx3-/- animals in immunization protocols with OMV. Animals were immunized with OMV (0.5–0.05 μg/ml) by ip or im injection, and serum was collected two weeks after the last immunization. Seven experiments were performed with 7–20 mice per group over a period of three years (Table 1). Fig. 5a shows the pooled data from experiments 1 to 5 (ip immunization) and Fig. 5b reports two representative experiments, one for each immunization route (experiments 6 and 7). Although there was considerable variability in serum bactericidal antibody (SBA) titers within experimental groups and from experiment to experiment, ptx3-deficiency was associated with a significant reduction in antibody production.

Bottom Line: PTX3-recognized microbial moieties are conserved structures which fulfil essential microbial functions.Administration of PTX3 reduced the bacterial load in infant rats challenged with Neisseria meningitidis.These results suggest that PTX3 recognizes a set of conserved structures from Neisseria meningitidis and acts as an amplifier/endogenous adjuvant of responses to this bacterium.

View Article: PubMed Central - PubMed

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

ABSTRACT
Long pentraxin 3 (PTX3) is a non-redundant component of the humoral arm of innate immunity. The present study was designed to investigate the interaction of PTX3 with Neisseria meningitidis. PTX3 bound acapsular meningococcus, Neisseria-derived outer membrane vesicles (OMV) and 3 selected meningococcal antigens (GNA0667, GNA1030 and GNA2091). PTX3-recognized microbial moieties are conserved structures which fulfil essential microbial functions. Ptx3-deficient mice had a lower antibody response in vaccination protocols with OMV and co-administration of PTX3 increased the antibody response, particularly in Ptx3-deficient mice. Administration of PTX3 reduced the bacterial load in infant rats challenged with Neisseria meningitidis. These results suggest that PTX3 recognizes a set of conserved structures from Neisseria meningitidis and acts as an amplifier/endogenous adjuvant of responses to this bacterium.

No MeSH data available.


Related in: MedlinePlus