The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps

J. Exp. Med. 204, 793-804 (2007)

Speaker: 李明翰                   Time: 15:10~16:00, Sep. 26, 2007

Commentator: 謝奇璋 醫師            Place: Room 601

Abstract:

Pattern recognition receptors (PRRs) play an important role in innate defense mechanism against pathogens. PRRs consist of cell-associated and soluble forms. Soluble PRRs include collectins, ficolins, and pentraxins (PTXs). PTX3, a member of PTXs superfamily, is produced by mononuclear phagocytes, myeloid dendritic cells and endothelial cells. PTX3 production is induced by primary inflammatory signals, such as IL-1, TNF-a and TLR engagement, and it binds with c1q, and selected pathogens such as Aspergillus fumigatus. Previous studies reported that ptx3^-/-mice are unable to recognize the conidia of A. fumigatus and fail to develop protective T helper cell type1 antifungal response. Neutrophils are also important in microbial killing. The authors want to known whether neutrophils produce PTX3. In this study, they found that PTX3 is stored in resting neutrophils and localized in specific (lactoferrin⁺ and lactoferrin/gelatinase⁺) granules. They also observed that microorganisms and TLR agonists triggered PTX3 secretion by neutrophils. Interestingly, released PTX3 can localize in neutrophil extracellular traps (NETs) which are composed of extruded DNA. They further investigated the function of PTX3 in neutrophils. Results showed that ptx3^-/- neutrophils have lower phagocytic activity as compared with wild-type. In addition, injection of wild-type neutrophils restored the phagocytic activity and provided the protective effect against A. fumigatus in ptx3^-/- mice. Thus, neutrophils represent a reservoir of PTX3 and release it in response to microbial or inflammatory signals.

References:

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2.         Garlanda, C. et al. Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature. 420, 182-186 (2002).