Fig 1.
Model of early olfactory immune response to N. fowleri infection.
(A) Water entry into the olfactory turbinates delivers N. fowleri to the olfactory epithelial surface. IgA, IgM, and IgG secreted within the airway potentially interfere with attachment to the epithelial surface, and the parasite is washed harmlessly away. (B) If this antibody response is insufficient, N. fowleri interaction with the olfactory surface results in an early (approximately 10 hours) and robust innate response. This early cellular response is characterized by inflammatory cell entry, particularly neutrophils, into the airway space, where they reduce the number of amoebas through effector mechanisms or mechanically inhibiting amoeba interaction with the epithelial surface. (C) When initial mechanisms fail to prevent parasite olfactory invasion, innate responses within the OE can be triggered. These responses involve macrophage and monocyte lineage cells but are again dominated by neutrophils. However, some parasites evade immune detection at this point, allowing them to continue invading deeper into the lamina propria. N. fowleri invasion of the lamina propria results in the parasite gaining entry into the olfactory nerve bundles. (D) These structures serve as conduits for OSNs axons to reach the brain, yet they now become a direct parasite pathway into the brain. Occasionally, innate cells will recognize amoeba within the axon bundles, but numerous amoebas make their way into the brain. (E) Once in the brain, N. fowleri proliferate and eventually provoke a massive inflammatory infiltration consisting of neutrophils, monocytes, and eosinophils that drives lethality. IgA, immunoglobulin A; IgG, immunoglobulin G; IgM, immunoglobulin M; IgM; N. fowleri, Naegleria fowleri; OE, olfactory epithelium; OSN, olfactory sensory neurons.
Table 1.