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Plasma membrane T oll‐like receptor activation increases bacterial uptake but abrogates endosomal Lactobacillus acidophilus induction of interferon‐ β
Author(s) -
Boye Louise,
Welsby Iain,
Lund Lisbeth Drozd,
Goriely Stanislas,
Frøkiær Hanne
Publication year - 2016
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12650
Subject(s) - endosome , lactobacillus acidophilus , chemistry , microbiology and biotechnology , receptor , lactobacillus , interferon γ , bacteria , biology , biochemistry , interferon gamma , in vitro , probiotic , fermentation , genetics
Summary Lactobacillus acidophilus induces a potent interferon‐ β ( IFN ‐ β ) response in dendritic cells ( DC s) by a Toll‐like receptor 2 ( TLR 2) ‐dependent mechanism, in turn leading to strong interleukin‐12 ( IL ‐12) production. In the present study, we investigated the involvement of different types of endocytosis in the L. acidophilus ‐induced IFN ‐ β and IL ‐12 responses and how TLR 2 or TLR 4 ligation by lipopolysaccharide and Pam3/4 CSK 4 influenced endocytosis of L. acidophilus and the induced IFN ‐ β and IL ‐12 production. Lactobacillus acidophilus was endocytosed by constitutive macropinocytosis taking place in the immature cells as well as by spleen tyrosine kinase (Syk) ‐dependent phagocytosis but without involvement of plasma membrane TLR 2. Stimulation with TLR 2 or TLR 4 ligands increased macropinocytosis in a Syk‐independent manner. As a consequence, incubation of DC s with TLR ligands before incubation with L. acidophilus enhanced the uptake of the bacteria. However, in these experimental conditions, induction of IFN ‐ β and IL ‐12 was strongly inhibited. As L. acidophilus‐ induced IFN ‐ β depends on endocytosis and endosomal degradation before signalling and as TLR stimulation from the plasma membrane leading to increased macropinocytosis abrogates IFN ‐ β induction we conclude that plasma membrane TLR stimulation leading to increased macropinocytosis decreases endosomal induction of IFN ‐ β and speculate that this is due to competition between compartments for molecules involved in the signal pathways. In summary, endosomal signalling by L. acidophilus that leads to IFN ‐ β and IL ‐12 production is inhibited by TLR stimulation from the plasma membrane.