Osteopontin binds and modulate the antibacterial action of eosinophil-recruiting chemokines during allergic inflammation

Presence of eosinophils in the airways is a hallmark of allergic asthma but several other asthmatic phenotypes exist including severe disease with a predominance of neutrophils. In addition to wheezing and dyspnea, there is also an increased risk of pneumoccal infections, in particular during severe asthma. Eosinophils can be recruited to the airways by chemokines including eotaxin-1/CCL11, eotaxin-2/CCL24, eotaxin-3/CCL26, RANTES/CCL5, and MEC/CCL28 that activate CCR3 on these cells. Several of these chemokines also have defensin-like antibacterial properties. Severe asthma is associated with high expression of the glycoprotein osteopontin in the airways. Osteopontin itself has neutrophil-recruiting properties and we hypothesized that this molecule can play roles in skewing the inflammatory profile during the course of asthma. OPN bound all eosinophil-recruiting chemokines with high affinity but less so to TSLP. In OVA-sensitized mice, administration of OPN had no direct effect on airway eosinophilia. The eosinophil-recruiting chemokines all displayed bactericidal activity against the common airway pathogen S. pneumoniae , but only CCL26 and CCL28 retained high antibacterial activity in the presence of sodium chloride (140 mM). Preincubation of the chemokines with osteopontin at eqimolar amounts strongly inhibited the antibacterial activity. The results suggest that osteopontin may impair host defense activities of the chemokines, increasing the vulnerability to acquire bacterial infections. In addition, osteopontin may lead to a different inflammatory subtype during the course of asthma through its ability to recruit neutrophils.