Broad and direct interaction between TLR and Siglec families of pattern recognition receptors and its regulation by Neu1
- Children's National Medical Center, United States
- University of California, Davis, United States
- St Jude Children's Research Hospital, United States
Figures
Figure 1
Extensive direct interactions between Siglecs and TLRs.
(A) Evaluation of TLR expression using TLR-primer set. Data shown are means and SEM of triplicate % of GAPDH levels. (B) and (C) Interactions between human (B) or mouse (C) SIGLEC-Fc fusion proteins …
Figure 2
Siglec-E negatively regulates production of inflammatory cytokines by DC in response to TLR ligands.
(A) and (B) Siglec-E inhibits production of IL-6 and TNFα by bone marrow derived DC. DC cultured from WT or Siglece−/− bone marrow were stimulated with indicated concentrations of LPS (A), or …
Figure 3
A critical role for Neu1 in Tlr4 activation.
(A) Siglec-E-Tlr4 association is disrupted by LPS stimulation. D2SC cells were cultured in the presence or absence of LPS overnight. Immunoprecipitation was used to test Siglec-E-Tlr4 association as …
Figure 4
A critical role for hematopoietic cell-expressed Neu1 in endotoxic shock.
(A) LPS stimulation in vivo increased cell surface Neu1 on DC, macrophage, and neutrophil. Data are representative of those from two independent experiments involving two mice per group. Splenocytes …
Figure 5
Sialidase inhibitors protect mice against endotoxic shock and preserve Siglec-TLR interactions.
(A) and (D) Survival analyses of mice that were treated with 450 µg/mouse of LPS (i.p., Escherichia coli 0111:B4). The mice received NeuAc2en and/or NeuGc2en (100 µg/mouse/injection) immediately …
Figure 6
NeuGc2en targets Neu1 to inhibit inflammation and confer protection against endotoxemia.
(A) Comparison of Neu5Ac2en and Neu5Gc2en for inhibitory activity against mouse Neu1-4. Lysates from 293T cells transiently transfected with murine Neu1-4 cDNA were assayed for sialidase activity in …
Figure 7
Exogenously added Neu5Gc2en inhibits cell surface but not intracellular Neu1.
(A) LPS stimulation increased sensitivity of Neu1 to exogenously added Neu5Gc2en. D2SC were transduced with lentiviral vectors encoding either scrambled or Neu1 shRNA and incubated with or without 1 …
Figure 8
Sialoside-based pattern recognition and self-nonself discrimination by the innate immune system.
TLR signaling is restrained by Siglecs that are either directly (such as Siglec-E) or indirectly through Cd24 (such Siglec-G) in the case of tissue injuries. Infections cause a positive feedback in …
