Lactobacillus reuteriSurface Mucus Adhesins Upregulate Inflammatory Responses Through Interactions With Innate C-Type Lectin Receptors.
The vertebrate gut symbiontLactobacillus reuteriexhibits strain-specific adhesion and health-promoting properties. Here, we investigated the role of the mucus adhesins, CmbA and MUB, upon interaction ofL. reuteriATCC PTA 6475 and ATCC 53608 strains with human monocyte-derived dendritic cells (moDCs). We showed that mucus adhesins increased the capacity ofL. reuteristrains to interact with moDCs and promoted phagocytosis. Our data also indicated that mucus adhesins mediate anti- and pro-inflammatory effects by the induction of interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), IL-1β, IL-6, and IL-12 cytokines.L. reuteriATCC PTA 6475 and ATCC 53608 were exclusively able to induce moDC-mediated Th1 and Th17 immune responses. We further showed that purified MUB activates moDCs and induces Th1 polarized immune responses associated with increased IFNγ production. MUB appeared to mediate these effectsviabinding to C-type lectin receptors (CLRs), as shown using cell reporter assays. Blocking moDCs with antibodies against DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) or Dectin-2 did not affect the uptake of the MUB-expressing strain, but reduced the production of TNF-α and IL-6 by moDCs significantly, in line with the Th1 polarizing capacity of moDCs. The direct interaction between MUB and CLRs was further confirmed by atomic force spectroscopy. Taken together these data suggest that mucus adhesins expressed at the cell surface ofL. reuteristrains may exert immunoregulatory effects in the gut through modulating the Th1-promoting capacity of DCs upon interaction with C-type lectins.
Department of Immunology, Faculty of Medicine, University of Debrecen Debrecen, Hungary.
Krisztián P
KP
Bene
The Gut Health and Food Safety Programme, Institute of Food Research Norwich, UK.
Devon W
DW
Kavanaugh
The Gut Health and Food Safety Programme, Institute of Food Research Norwich, UK.
Charlotte
C
Leclaire
The Gut Health and Food Safety Programme, Institute of Food Research Norwich, UK.
Allan P
AP
Gunning
The Gut Health and Food Safety Programme, Institute of Food Research Norwich, UK.
Donald A
DA
MacKenzie
Food and Health Programme, Institute of Food Research Norwich, UK.
Alexandra
A
Wittmann
Food and Health Programme, Institute of Food Research Norwich, UK.
Ian D
ID
Young
Food and Health Programme, Institute of Food Research Norwich, UK.
Norihito
N
Kawasaki
Department of Immunology, Faculty of Medicine, University of Debrecen Debrecen, Hungary.
Eva
E
Rajnavolgyi
The Gut Health and Food Safety Programme, Institute of Food Research Norwich, UK.
Nathalie
N
Juge
C-type lectins; DC-SIGN; Dectin-2; L. reuteri; T-lymphocytes; dendritic cells; mucus adhesins; probiotic