Milk Matters: Soluble Toll-Like Receptor 2

The majority of infants who breastfeed from their HIV-positive mothers remain uninfected despite constant and repeated exposure to virus over weeks to years. This phenomenon is not fully understood but has been closely linked to innate factors in breast milk (BM). Most recently we have focused on on...

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Veröffentlicht in:PloS one 2012-07, Vol.7 (7), p.e40138
Hauptverfasser: Henrick, Bethany M, Nag, Kakon, Yao, Xiao-Dan, Drannik, Anna G, Aldrovandi, Grace M, Rosenthal, Kenneth L
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Sprache:eng
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Zusammenfassung:The majority of infants who breastfeed from their HIV-positive mothers remain uninfected despite constant and repeated exposure to virus over weeks to years. This phenomenon is not fully understood but has been closely linked to innate factors in breast milk (BM). Most recently we have focused on one such innate factor, soluble Toll-like receptor 2 (sTLR2) for its significant contribution as an inhibitor of inflammation triggered by bacterial and viral antigens. We hypothesized that sTLR2 in BM inhibits immune activation/inflammation and HIV-1 infection. sTLR2 protein profiles were analyzed in HIV-uninfected BM and showed dramatic variability in expression concentration and predominant sTLR2 forms between women. sTLR2 immunodepleted BM, versus mock-depleted BM, incubated with Pam.sub.3 CSK.sub.4 lead to significant increases in IL-8 production in a TLR2-dependant fashion in U937, HEK293-TLR2, and Caco-2. Importantly, TLR2-specific polyclonal and monoclonal antibody addition to BM prior to cell-free R5 HIV-1 addition led to significantly (P
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0040138