PRELP Enhances Host Innate Immunity against the Respiratory Tract Pathogen .

Respiratory tract infections are one of the leading causes of mortality worldwide urging better understanding of interactions between pathogens causing these infections and the host. Here we report that an extracellular matrix component proline/arginine-rich end leucine-rich repeat protein (PRELP) is a novel antibacterial component of innate immunity. We detected the presence of PRELP in human bronchoalveolar lavage fluid and showed that PRELP can be found in alveolar fluid, resident macrophages/monocytes, myofibroblasts, and the adventitia of blood vessels in lung tissue. PRELP specifically binds respiratory tract pathogens , , and , but not other bacterial pathogens tested. We focused our study on and found that PRELP binds the majority of clinical isolates of ( = 49) through interaction with the ubiquitous surface protein A2/A2H. usually resists complement-mediated serum killing by recruiting to its surface a complement inhibitor C4b-binding protein, which is also a ligand for PRELP. We found that PRELP competitively inhibits binding of C4b-binding protein to bacteria, which enhances membrane attack complex formation on and thus leads to increased serum sensitivity. Furthermore, PRELP enhances phagocytic killing of serum-opsonized by human neutrophils in vitro. Moreover, PRELP reduces adherence to and invasion of human lung epithelial A549 cells. Taken together, PRELP enhances host innate immunity against through increasing complement-mediated attack, improving phagocytic killing activity of neutrophils, and preventing bacterial adherence to lung epithelial cells.