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Bile salt-stimulated lipase from human milk binds DC-SIGN and inhibits human immunodeficiency virus type 1 transfer to CD4+ T cells.

ABSTRACT: A wide range of pathogens, including human immunodeficiency virus type 1 (HIV-1), hepatitis C virus, Ebola virus, cytomegalovirus, dengue virus, Mycobacterium, Leishmania, and Helicobacter pylori, can interact with dendritic cell (DC)-specific ICAM3-grabbing nonintegrin (DC-SIGN), expressed on DCs and a subset of B cells. More specifically, the interaction of the gp120 envelope protein of HIV-1 with DC-SIGN can facilitate the transfer of virus to CD4+ T lymphocytes in trans and enhance infection. We have previously demonstrated that a multimeric LeX component in human milk binds to DC-SIGN, preventing HIV-1 from interacting with this receptor. Biochemical analysis reveals that the compound is heat resistant, trypsin sensitive, and larger than 100 kDa, indicating a specific glycoprotein as the inhibitory compound. By testing human milk from three different mothers, we found the levels of DC-SIGN binding and viral inhibition to vary between samples. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and matrix-assisted laser desorption ionization analysis, we identified bile salt-stimulated lipase (BSSL), a Lewis X (LeX)-containing glycoprotein found in human milk, to be the major variant protein between the samples. BSSL isolated from human milk bound to DC-SIGN and inhibited the transfer of HIV-1 to CD4+ T lymphocytes. Two BSSL isoforms isolated from the same human milk sample showed differences in DC-SIGN binding, illustrating that alterations in the BSSL forms explain the differences observed. These results indicate that variations in BSSL lead to alterations in LeX expression by the protein, which subsequently alters the DC-SIGN binding capacity and the inhibitory effect on HIV-1 transfer. Identifying the specific molecular interaction between the different forms may aid in the future design of antimicrobial agents.

SUBMITTER: Naarding MA

PROVIDER: S-EPMC1610064 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature

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Bile salt-stimulated lipase from human milk binds DC-SIGN and inhibits human immunodeficiency virus type 1 transfer to CD4+ T cells.

Naarding Marloes A MA Dirac Annette M AM Ludwig Irene S IS Speijer Dave D Lindquist Susanne S Vestman Eva-Lotta EL Stax Martijn J MJ Geijtenbeek Teunis B H TB Pollakis Georgios G Hernell Olle O Paxton William A WA

Antimicrobial agents and chemotherapy 20061001 10

A wide range of pathogens, including human immunodeficiency virus type 1 (HIV-1), hepatitis C virus, Ebola virus, cytomegalovirus, dengue virus, Mycobacterium, Leishmania, and Helicobacter pylori, can interact with dendritic cell (DC)-specific ICAM3-grabbing nonintegrin (DC-SIGN), expressed on DCs and a subset of B cells. More specifically, the interaction of the gp120 envelope protein of HIV-1 with DC-SIGN can facilitate the transfer of virus to CD4+ T lymphocytes in trans and enhance infection ...[more]

PMID: 17005819

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Project description:Breast milk contains bile salt-stimulated lipase (BSSL), which significantly increases the fat digestion capacity of newborns who have limited pancreatic lipase secretion in the first few months after birth. Problematically, Holder pasteurization used in non-profit milk banks to ensure the microbiological safety of donor milk for infants, particularly preterm infants (<37 weeks gestation age), destroys milk BSSL, thus limiting infant fat absorption capacity. Alternative strategies are needed to ensure the safety of donor milk while preserving BSSL activity. Three alternative pasteurization techniques-high-pressure processing (HPP, 550 MPa, 5 min), gamma cell irradiation (IR, 2.5 Mrads) and UV-C (254 nm, 0-33,000 J/L)-were compared with Holder pasteurization (low-temperature long-time, LTLT, 62.5°C, 30 min) for retention of BSSL activity in donor breast milk. As the time required for donor milk pasteurization by UV-C in published methods was not clear, donor breast milk was spiked with seven common bacterial strains and treated by UV-C for variable time periods and the minimum UV-C dosage required to achieve a 5-log10 reduction of CFU/mL was determined. Eight thousand two hundred fifty J/L of UV-C exposure was sufficient to achieve 5-log10 reduction of each of bacterial targets, including Bacillus and Paenibacillus spores. The retention of BSSL activity was highest after HPP (retaining 62% of the untreated milk BSSL activity), followed by UV-C (16,500 J/L), IR and LTLT (35, 29, and 0.3% retention, respectively). HPP was an effective alternative to pasteurize milk with improved retention of BSSL activity compared to Holder pasteurization. Future work should investigate the effect of alternative pasteurization techniques on the entire array of bioactive components in donor breast milk and how these changes affect preterm infant health outcomes. Implementation of HPP technique at milk banks could improve donor milk-fed infant fat absorption and growth.

Dataset Information

Bile salt-stimulated lipase from human milk binds DC-SIGN and inhibits human immunodeficiency virus type 1 transfer to CD4+ T cells.

Publications

Bile salt-stimulated lipase from human milk binds DC-SIGN and inhibits human immunodeficiency virus type 1 transfer to CD4+ T cells.

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