Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)

First Advisor

Co-Robin M. Overstreet

Second Advisor

Ronald L. Thune


Calyptospora funduli is a pathogenic coccidium that infects the liver and pancreas of estuarine killifishes belonging to the genus Fundulus. Experimental infection of the atypical fish host Rivulus marmoratus with this intracellular protozoan parasite caused the development of hepatic macrophage aggregates (MA's) and granulomas. The Rivulus/Calyptospora host-parasite system thus represents a new laboratory model for investigations of MA biology. In the present study, this model was used to: (1) examine the morphology and sequential development of the parasite-elicited hepatic MA's in R. marmoratus, (2) define the role that these structures play in the pathogenesis of an infectious disease process, and (3) quantify effects of a selected chemical toxicant on MA, granuloma, and parasite development using morphometric analysis. Histopathological evaluation of R. marmoratus at various time intervals following experimental infection indicates that parasite-elicited hepatic MA's and granulomas represent endstages of a chronic inflammatory process in which a mononuclear phagocyte, apparently derived from the peripheral circulation, plays a prominent role. MA formation is initiated during the gamogonic development of the parasite in response to degenerating gamonts and necrosis of hepatocytes. Granulomas are elicited during sporogony and develop in response to the oocyst stage of the parasite. Sequential histochemical analysis of developing MA's indicates that most of the pigment that is sequestered by these structures is the lipogenic substance ceroid. Melanin is present but not abundant. Ultrastructural analysis of parasite-elicited hepatic MA's suggests that the sequestered pigments are lysosomally derived. Pigment granules are lysosomal residual bodies that are retained by macrophages after the intracellular digestion of phagocytosed host and parasite-derived debris. In addition to the mononuclear phagocyte, five other morphologically distinct leukocytes are associated with the inflammatory response leading to MA and granuloma formation. Ultrastructurally, the parasite-elicited hepatic MA's resemble those that occur in the spleen and kidney of this species. Exposure of experimentally infected fish to cadmium chloride for 50 days suppressed parasite development and caused a reduction in the number and size of the MA's and granulomas. Cadmium did not measurably affect macrophage function at the tested exposure concentration.