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Binding of human milk to pathogen receptor DC-SIGN varies with bile salt-stimulated lipase (BSSL) gene polymorphism.

Stax MJ, Naarding MA, Tanck MW, Lindquist S, Hernell O, Lyle R, Brandtzaeg P, Eggesbø M, Pollakis G, Paxton WA - PLoS ONE (2011)

Bottom Line: Objective was to study variation in DC-SIGN binding properties and the relation between DC-SIGN binding capacity of milk and BSSL gene polymorphisms.DC-SIGN binding properties were highly variable for milks derived from different mothers and between samplings from different geographical regions.Differences in DC-SIGN binding were correlated with a genetic polymorphism in BSSL which is related to the number of 11 amino acid repeats at the C-terminus of the protein.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Objective: Dendritic cells bind an array of antigens and DC-SIGN has been postulated to act as a receptor for mucosal pathogen transmission. Bile salt-stimulated lipase (BSSL) from human milk potently binds DC-SIGN and blocks DC-SIGN mediated trans-infection of CD4(+) T-lymphocytes with HIV-1. Objective was to study variation in DC-SIGN binding properties and the relation between DC-SIGN binding capacity of milk and BSSL gene polymorphisms.

Study design: ELISA and PCR were used to study DC-SIGN binding properties and BSSL exon 11 size variation for human milk derived from 269 different mothers distributed over 4 geographical regions.

Results: DC-SIGN binding properties were highly variable for milks derived from different mothers and between samplings from different geographical regions. Differences in DC-SIGN binding were correlated with a genetic polymorphism in BSSL which is related to the number of 11 amino acid repeats at the C-terminus of the protein.

Conclusion: The observed variation in DC-SIGN binding properties among milk samples may have implications for the risk of mucosal transmission of pathogens during breastfeeding.

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Related in: MedlinePlus

DC-SIGN binding capacity correlates to BSSL genotype.Alleles are defined as L (9 to 15 repeats) or H (16–19 repeats). The BSSL genotype is plotted against DC-SIGN affinity for mothers from the Netherlands, Sweden, Norway and Egypt. LL, LH and HH genotypes are plotted against DC-SIGN binding. Median DC-SIGN binding within cohorts is indicated by a horizontal line.
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pone-0017316-g004: DC-SIGN binding capacity correlates to BSSL genotype.Alleles are defined as L (9 to 15 repeats) or H (16–19 repeats). The BSSL genotype is plotted against DC-SIGN affinity for mothers from the Netherlands, Sweden, Norway and Egypt. LL, LH and HH genotypes are plotted against DC-SIGN binding. Median DC-SIGN binding within cohorts is indicated by a horizontal line.

Mentions: Differences in BSSL protein size were linked to the DC-SIGN binding properties of milk (figure 1c). In addition, we hypothesized that variation in DC-SIGN binding may be caused by size differences in the VNTR domain of the BSSL gene. To test this possibility we compared VNTR domain sizes with DC-SIGN binding potency of the corresponding milks. The majority of tested mothers have at least one allele with 16 repeats whereas the non-16 repeat BSSL variants mostly have less than 16 repeats (see figure 3b). We arbitrarily defined less than 16 repeats as low (L) and 16 or more repeats as high (H) repeat number. Mothers have either two low (LL), one allele with low and one with high (LH) or two alleles with high repeat numbers (HH). The BSSL repeat number has a significant (p = 0.018) effect on the DC-SIGN binding capacity for all 4 tested cohorts (figure 4a). In the 3 European cohorts we found that mothers with the LH genotype had significantly stronger DC-SIGN binding milk (p = 0.016) than mothers with the HH genotype. These LH mothers also had marginally significant stronger DC-SIGN binding milk (p = 0.064) than mothers with the LL genotype. The LL genotype reaches low frequencies, as the majority of individuals carry at least 1 allele with high repeat numbers (figure 3c). The H-repeat group (n = 353) mainly exists of 16 repeat BSSL alleles (n = 303) and only 50 alleles having more than 16 repeats. Alleles with more than 16 repeats are mainly found in the Norwegian population (n = 41).


Binding of human milk to pathogen receptor DC-SIGN varies with bile salt-stimulated lipase (BSSL) gene polymorphism.

Stax MJ, Naarding MA, Tanck MW, Lindquist S, Hernell O, Lyle R, Brandtzaeg P, Eggesbø M, Pollakis G, Paxton WA - PLoS ONE (2011)

DC-SIGN binding capacity correlates to BSSL genotype.Alleles are defined as L (9 to 15 repeats) or H (16–19 repeats). The BSSL genotype is plotted against DC-SIGN affinity for mothers from the Netherlands, Sweden, Norway and Egypt. LL, LH and HH genotypes are plotted against DC-SIGN binding. Median DC-SIGN binding within cohorts is indicated by a horizontal line.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046167&req=5

pone-0017316-g004: DC-SIGN binding capacity correlates to BSSL genotype.Alleles are defined as L (9 to 15 repeats) or H (16–19 repeats). The BSSL genotype is plotted against DC-SIGN affinity for mothers from the Netherlands, Sweden, Norway and Egypt. LL, LH and HH genotypes are plotted against DC-SIGN binding. Median DC-SIGN binding within cohorts is indicated by a horizontal line.
Mentions: Differences in BSSL protein size were linked to the DC-SIGN binding properties of milk (figure 1c). In addition, we hypothesized that variation in DC-SIGN binding may be caused by size differences in the VNTR domain of the BSSL gene. To test this possibility we compared VNTR domain sizes with DC-SIGN binding potency of the corresponding milks. The majority of tested mothers have at least one allele with 16 repeats whereas the non-16 repeat BSSL variants mostly have less than 16 repeats (see figure 3b). We arbitrarily defined less than 16 repeats as low (L) and 16 or more repeats as high (H) repeat number. Mothers have either two low (LL), one allele with low and one with high (LH) or two alleles with high repeat numbers (HH). The BSSL repeat number has a significant (p = 0.018) effect on the DC-SIGN binding capacity for all 4 tested cohorts (figure 4a). In the 3 European cohorts we found that mothers with the LH genotype had significantly stronger DC-SIGN binding milk (p = 0.016) than mothers with the HH genotype. These LH mothers also had marginally significant stronger DC-SIGN binding milk (p = 0.064) than mothers with the LL genotype. The LL genotype reaches low frequencies, as the majority of individuals carry at least 1 allele with high repeat numbers (figure 3c). The H-repeat group (n = 353) mainly exists of 16 repeat BSSL alleles (n = 303) and only 50 alleles having more than 16 repeats. Alleles with more than 16 repeats are mainly found in the Norwegian population (n = 41).

Bottom Line: Objective was to study variation in DC-SIGN binding properties and the relation between DC-SIGN binding capacity of milk and BSSL gene polymorphisms.DC-SIGN binding properties were highly variable for milks derived from different mothers and between samplings from different geographical regions.Differences in DC-SIGN binding were correlated with a genetic polymorphism in BSSL which is related to the number of 11 amino acid repeats at the C-terminus of the protein.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Objective: Dendritic cells bind an array of antigens and DC-SIGN has been postulated to act as a receptor for mucosal pathogen transmission. Bile salt-stimulated lipase (BSSL) from human milk potently binds DC-SIGN and blocks DC-SIGN mediated trans-infection of CD4(+) T-lymphocytes with HIV-1. Objective was to study variation in DC-SIGN binding properties and the relation between DC-SIGN binding capacity of milk and BSSL gene polymorphisms.

Study design: ELISA and PCR were used to study DC-SIGN binding properties and BSSL exon 11 size variation for human milk derived from 269 different mothers distributed over 4 geographical regions.

Results: DC-SIGN binding properties were highly variable for milks derived from different mothers and between samplings from different geographical regions. Differences in DC-SIGN binding were correlated with a genetic polymorphism in BSSL which is related to the number of 11 amino acid repeats at the C-terminus of the protein.

Conclusion: The observed variation in DC-SIGN binding properties among milk samples may have implications for the risk of mucosal transmission of pathogens during breastfeeding.

Show MeSH
Related in: MedlinePlus