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

<p>NTHI (dark green bacteria) asymptomatically colonizes the heme-iron sufficient nasopharynx epithelium (orange cells) (<b>A</b>). 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>B</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 (<b>C</b>).</p>