Figure 10. Model of CR3-mediated immune suppression and crosstalk with TLR2 signaling during the phagocytosis of Schu S4 by human macrophages.

In the absence of serum, pathogen associated molecular determinants such as lipoproteins will be recognized by TLR2 which activates MAP kinase (ERK1/2 and p38) and NF-κB signaling pathways, and induces host pro-inflammatory responses. Phagocytosis is limited without the optimal engagement of CR3. In the presence of serum C3bi is deposited on the Ft Schu S4 surface, which optimally engages CR3 and enhances phagocytosis. At the same time, TLR2 is activated at least to some degree, leading to inside-out activation of CR3, which contributes to enhanced outside-in CR3 signaling and increased phagocytosis. CR3-mediated signaling activates Lyn and AKT, and leads to an increased MKP-1 level which results in inhibition of MAPK activity. This allows for increased phagocytosis simultaneously with a dampened host immune response.