Histoplasma capsulatum and Caenorhabditis elegans: a simple nematode model for an innate immune response to fungal infection.

Histoplasma capsulatum is a primary fungal pathogen of mammals responsible for histoplasmosis. During pathogenesis H. capsulatum yeast proliferate in phagosomes of macrophages. This extensive host/pathogen interaction involves a complex cascade of responses in both organisms. In the mammalian host, infection results in complex branched immunity that is initiated with an innate response and later induces an adaptive response but each response is difficult to resolve during fungal infection. Therefore, in an effort to identify less complex systems and to gain understanding of the host innate response to H. capsulatum, we constructed a mini-host survival assay. With this assay, we found ingestion of virulent Histoplasma capsulatum NAm 1 strain yeasts to be lethal to a Bristol-N2 Caenorhabditis elegans host. The virulent H. capsulatum NAm1 strain shows differential lethality under live/heat-killed infective conditions. Specifically, after ingestion of live yeast lethality is > or = 90% within 48 to 72 h, whereas worms ingesting heat-killed yeast reach equivalent mortality only after 10-14 days. On the other hand, ingestion of live H. capsulatum yeast of the nonvirulent NAm 1 (ura(-)) strain is no more lethal to the nematode than heat-killed yeast. Therefore, C. elegans provides an attractive model for further investigations of the ancient innate immune response during early host/pathogen (H. capsulatum/worm) interaction and pathogenesis.