Bile salt-stimulated lipase from human milk and mucosal transmission of pathogens during breastfeeding
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Human milk contains an array of antimicrobial products that can interfere with pathogens being transmitted from mothers to their infants during breastfeeding. In this chapter we specifically discuss factors that can influence human immonodeficiency virus type-1 (HIV-1) transmission. We discuss the potential mechanisms through which HIV-1 can cross a mucosal barrier and the array of cell types involved with such a mechanism. One of the major cells proposed to be involved with transmission are dendritic cells (DCs) which express an array of receptors which carry the potential to interact with pathogen antigens as well as whole pathogens. The C-type lectin DC-specific ICAM-3 grabbing non-intergrin (DC-SIGN) has specifically been postulated to mediate mucosal transmission of HIV-1. The gp120 envelope protein of HIV-1 can interact with DC-SIGN and promote pathogen capture and uptake and subsequent presentation of virus to CD4+ T-lymphocytes, through a mechanism known as trans-infection. HIV-1 is not the only pathogen known to bind DC-SIGN and this mechanism in all likelihood involved in transmission of a number of viruses, bacteria and fungi. Factors in human milk with the potential to modulate pathogen capture would therefore have the capacity to influence transmission. We have shown that a human glycoprotein found in human milk, bile salt-stimulated lipase, can potently bind DC-SIGN and prevent HIV-1 capture and transfer to CD4+ T-lymphocytes. This protein is composed of a variable number of 11 amino acid repeats at the C-terminus and this variation can be associated with strength of binding DC-SIGN. Factors with similar activity have also been identified in other bodily fluids suggesting that we have evolved ways of interfering with pathogen transmission across a mucosal surface. Since DCs are modulators of immune responses it is tempting to speculate that such factors skew immunity towards a desired response beneficial for the exposed host.