First Author | Boye L | Year | 2016 |
Journal | Immunology | Volume | 149 |
Issue | 3 | Pages | 329-342 |
PubMed ID | 27441725 | Mgi Jnum | J:246956 |
Mgi Id | MGI:5922477 | Doi | 10.1111/imm.12650 |
Citation | Boye L, et al. (2016) Plasma membrane Toll-like receptor activation increases bacterial uptake but abrogates endosomal Lactobacillus acidophilus induction of interferon-beta. Immunology 149(3):329-342 |
abstractText | Lactobacillus acidophilus induces a potent interferon-beta (IFN-beta) response in dendritic cells (DCs) by a Toll-like receptor 2 (TLR2) -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-beta and IL-12 responses and how TLR2 or TLR4 ligation by lipopolysaccharide and Pam3/4CSK4 influenced endocytosis of L. acidophilus and the induced IFN-beta 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 TLR2. Stimulation with TLR2 or TLR4 ligands increased macropinocytosis in a Syk-independent manner. As a consequence, incubation of DCs with TLR ligands before incubation with L. acidophilus enhanced the uptake of the bacteria. However, in these experimental conditions, induction of IFN-beta and IL-12 was strongly inhibited. As L. acidophilus-induced IFN-beta depends on endocytosis and endosomal degradation before signalling and as TLR stimulation from the plasma membrane leading to increased macropinocytosis abrogates IFN-beta induction we conclude that plasma membrane TLR stimulation leading to increased macropinocytosis decreases endosomal induction of IFN-beta 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-beta and IL-12 production is inhibited by TLR stimulation from the plasma membrane. |