Proposed model for host-mediated nutritional environment effects on NTHI pathogenesis.

NTHI (dark green bacteria) asymptomatically colonizes the heme-iron sufficient nasopharynx epithelium (orange cells) (A). Permissive factors promote ascension up the Eustachian tube to the intact middle ear epithelium (brown cells) where NTHI are heme-iron restricted (light green bacteria) (B). Disease progression results in infiltration of red blood cells (red circle), immune cells (gray circle) and expansion of interstitial space (open circles) leading to potential heme-iron sources (red hexagon) for NTHI (dark green bacteria). This transition from heme-iron restricted to replete microenvironments primes NTHI to alter morphology and enhance biofilm formation, both of which promote invasion and persistence (C).