AUTHOR=Mathiesen Ronja , Eld Helene M. S. , Sørensen Juliane , Fuglsang Eva , Lund Lisbeth Drozd , Taverniti Valentina , Frøkiær Hanne 

TITLE=Mannan Enhances IL-12 Production by Increasing Bacterial Uptake and Endosomal Degradation in L. acidophilus and S. aureus Stimulated Dendritic Cells

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.02646

DOI=10.3389/fimmu.2019.02646

ISSN=1664-3224

ABSTRACT=<p>The mannose receptor (MR) is a C-type lectin involved in endocytosis and with a poorly defined ability to modulate cellular activation. We investigated the effect of mannan treatment prior to stimulation of murine bone marrow-derived dendritic cells with the Gram-positive bacteria <italic>Lactobacillus acidophilus</italic> NCFM <italic>(L. acidophilus</italic>) on the induction of Interleukin (IL)-12. Mannan enhanced the IL-12 production induced by <italic>L. acidophilus</italic> in a dose dependent manner (up to 230% enhancement). Additionally, mannan-enhanced IL-12 induction was also demonstrated with another Gram-positive bacteria, <italic>Staphylococcus aureus (S. aureus)</italic>, while an IL-12 reducing effect was seen on <italic>Escherichia coli</italic> stimulated cells. Furthermore, the expression of Interferon β (<italic>Ifnb</italic>) was increased in cells treated with mannan prior to stimulation with <italic>L. acidophilus</italic>. The addition of mannan but not of bacteria led to endocytosis of MR, while addition of mannan prior to <italic>L. acidophilus</italic> or <italic>S. aureus</italic> resulted in increased endocytosis of bacteria, a faster killing of endocytosed bacteria, and increased reactive oxygen species production. Expression of signaling lymphocytic activation molecule (SLAMF)1 shown previously to be involved in the facilitation of endosomal degradation was upregulated by mannan but not by <italic>L. acidophilus</italic> and <italic>S. aureus</italic>. The IL-12 enhancement by mannan but not the IL-12 induced by the bacteria was abrogated by addition of inhibitors of clathrin coated pits (chlorpromazine and monodansylcadaverine). Furthermore, the addition of acid sphingomyelinase, a facilitator of ceramide raft formation, prior to addition of <italic>L. acidophilus</italic> enhanced the IL-12 production and the endocytosis of bacteria. In summary, our results show that mannan increases the IL-12 production induced by some Gram-positive bacteria through MR-endocytosis, which increases bacterial endocytosis and endosomal killing. The differential effect of MR activation on the IL-12 production induced by Gram-positive and Gram-negative bacteria may influence the immune response toward allergens and other glycoproteins.</p>