Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum

Patton, John B.; Bennuru, Sasisekhar; Eberhard, Mark L.; Hess, Jessica A.; Torigian, April; Lustigman, Sara; Nutman, Thomas B.; Abraham, David

Genetic traits can play a significant role in the susceptibility of animals to infection as has been clearly demonstrated by the diversity of susceptibility of different mouse strains to infection with Litomosoides sigmodontis [59] . The CC mouse project was developed to produce an extremely diverse set of inbred animals that could be used for mapping different genetic traits [57] . Five different CC mouse strains, selected based on their diverse genetic backgrounds, were tested for susceptibility to O. volvulus and were completely resistant to the infection. This observation suggests that either mice are missing some integral factors required for parasite growth or the immune responses in mice are effective at eliminating the infection. The question remains as to why parasites are recovered live from diffusion chambers implanted in mice but not when injected into the tissues. There are several possible explanations including: (1) the diffusion chamber acts as a barrier from the immune response creating an immune privileged site, (2) the larvae within the diffusion chamber are blocked from migrating through the tissue releasing excretory and secretory products and thereby eliciting an immune reaction, or (3) the diffusion chamber attracts host components to the parasite microenvironment that are beneficial for parasite development.