Adherence to AECs
Having bypassed MCC defenses, NTHi employs multiple
surface-expressed multifunctional adhesion proteins, such as proteins E
and F, that bind to nonciliated AECs and extracellular matrix (ECM)
proteins, in particular laminin and vitronectin. Adherence is enhanced
when there is structural damage to the airway mucosa from viral
infections or chronic inflammation exposing ECM proteins. The trimeric
autotransporters, Hi adhesin (Hia), Hi adhesion protein (Hap), and
high–molecular weight (HMW) proteins 1 and 2, play an important role in
colonization, even though only Hap is highly conserved in NTHistrains. Moreover, the type IV pili on NTHi cell surfaces mediate
adherence to AECs by interacting with the intracellular adhesion
molecule-1 (ICAM-1), which also serves as a cellular receptor for
rhinoviruses that may help explain their frequent co-infections. The
ICAM-1 receptors on the AEC surface increase in numbers in COPD
patients, in smokers, and exhibit a positive feedback loop followingNTHi exposure. Additionally, P1 fimbriae bind to the
carcinoembryonic antigen-related
cell adhesion molecule (CEACAM-1), while P5 fimbriae adhere to both
CEACAM-1 and ICAM-1 on AEC surfaces,
respectively.59,60 As well as binding to mucins, other
OMPs adhere to exposed ECM proteins.61 Indeed, the
interaction between the ECM exposed within the COPD airway environment
and Hap facilitates NTHi attachment to AECs and this interaction
may also operate in the lungs of children with CSLD.