Pathogenic Bacteria Colonizing the Airways in Asymptomatic Neonates Stimulates Topical Inflammatory Mediator Release

ABSTRACT RATIONALE: Bacterial colonization of neonatal airways with the pathogenic bacterial species M. catarrhalis, S. pneumoniae and H. influenzae is associated with later development of childhood asthma. OBJECTIVE: To study a possible association between the immune signature of the upper airways and colonization with pathogenic bacterial strains in healthy neonates. Method: 20 cytokines and chemokines were quantified in vivo in the airway mucosal lining fluid of 662 neonates from the COPSAC2010 birth cohort. Colonization of the hypopharynx with M. catarrhalis, S. pneumoniae, H. influenzae and S. aureus was assessed simultaneously. The association between immune signatures and bacterial colonization or non-colonized controls was analyzed utilizing conventional statistical methods supplemented by a multivariate approach for pattern identification. MEASUREMENTS AND MAIN RESULTS: Colonization with M. catarrhalis and H. influenzae induced a mixed Th1/Th2/Th17-type response with high levels of IL-1β (M. catarrhalis P= 2.2x10-12, H. influenzae P= 7.1x10-10), TNF-α (M. catarrhalis P= 1.5x10-9, H. influenzae P= 5.9x10-7) and MIP-1β (M. catarrhalis P= 1.6x10-11, H. influenzae P= 2.7x10-7). S. aureus colonization demonstrated a Th17-promoting profile with elevated IL-17 levels (P=1.6x10-24). S. pneumoniae colonization was not significantly associated with any of the mediators. CONCLUSION: M. catarrhalis and H. influenzae colonization of the airways of asymptomatic neonates is associated with an inflammatory immune response profile of the airway mucosa which may result in chronic inflammation.