PTX3, a humoral pattern recognition molecule at the interface between microbe and matrix recognition

•PTX3 acts as an extrinsic oncosuppressor gene.•PTX3 tunes complement-mediated, macrophage-sustained, tumor promoting inflammation.•An acidic pH sets the PTX3 molecule in a tissue repair mode.•Matrix and microbial recognition are related functions in evolution.

Innate immunity consists of a cellular and a humoral arm. PTX3 is a fluid patter recognition molecule (PRM) with antibody-like properties. Gene targeted mice and genetic associations in humans suggest that PTX3 plays a non-redundant role in resistance against selected pathogens (e.g. Aspergillus fumigatus, Pseudomonas aeruginosa, uropathogenic Escherichia coli) and in the regulation of inflammation. PTX3 acts as an extrinsic oncosuppressor by taming complement elicited tumor-promoting inflammation. Recent results indicate that, by interacting with provisional matrix components, PTX3 contributes to the orchestration of tissue repair. An acidic pH sets PTX3 in a tissue repair mode, while retaining anti-microbial recognition. Based on these data and scattered information on humoral PRM and matrix components, we surmise that matrix and microbial recognition are related functions in evolution.