Host cell actin remodeling in response to cryptosporidium

Despite sporadic reports of Cryptosporidium infection throughout the 1900s, the clinical significance of this parasite in humans was not recognized until the first documented human diagnosis of C parvum in 1976,^1,2 and the subsequent realization that as an opportunistic infectious agent, Cryptosporidium infection in AIDS patients was associated with sijgnificant morbidity and mortality^3,4 and a causative agent of AIDS-related biliary disease.^5-7 With the advent of highly active antiretroviral therapy, AIDS-related cryptosporidial disease occurs less frequently, yet Cryptosporidium is now recognized as a widely dispersed parasite and a significant enteropathogen of immunocompetent and immunocompromised hosts. Two species, C. hominis and C parvum, readily infect humans. While C. parvum infects a wide range of mammalian hosts, C hominis is believed to infect only humans. Most of the experimental evidence of host cell actin remodeling to date has been accomplished using C parvum. C parvum exhibits a monoxenous life cycle, where all developmental stages occur in a single host. The infective cycle begins when a vertebrate host ingests an oocyst. C parvum oocysts excyst in the gastrointestinal tract, releasing infective sporozoites that invade the enteric epithelium. It is these infective sporozoites that have been utilized to look at the initial cascade of events culminating in actin reorganization in cell cultm-e systems. Once internalized at the surface of epithelial cells, the trophozoite undergoes asexual reproduction by merogony forming a Type-1 meront. Six to eight Type-1 merozoites are released from Type-1 meronts when mature; they then invade neighboring enterocytes. Ultrastructurally, internalization of sporozoites and merozoites is similar and it is assumed that both distinct developmental stages utilize the same invasion machinery and drive actin reorganization through similar mechanisms. Less is known about host cell actin reorganization during the sexual stages of parasite development. Therefore, the current brief summary will focus on actin reorganization during zoite internalization and development, focusing primarily on the molecular mechanisms of actin reorganization.