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of infections caused by the Stramenopilan Oomycete pathogen Pythium insidiosum |
| This fungal-like organism causes pythiosis, a life threatening disease in humans and other animals in the tropical and subtropical areas of the world including the USA. During the past 10 years we have studied its in vitro life cycle, introduced several immunological diagnostic assays, and developed an immunotherapeutic vaccine to treat the disease. The laboratory research efforts have centered on this curative vaccine that has already saved the lives of several hundred horses, and at least five out of eight humans with terminal pythiosis in their arteries. Our hypothesis is that the therapeutic vaccine works by switching the TH2 response, in place during natural infection, to a TH1 protective immunity. Several lines of evidence support this tenet. For instance, after vaccination the eosinophilic inflammatory reaction, typical of the diseases, changes to a mononuclear response (macrophages and lymphocytes). Moreover, our preliminary data showed that IL4 is always present during pythiosis. However, after vaccination an increase of IL2 and a decrease of IL4 are found in cured human patients. We believe that the down regulation of the TH2 subset and activation of the TH1 response are behind the vaccine's curative properties. Presently, we are investigating this hypothesis in an animal model and characterizing the P. insidiosum's genes that encode the immunogens involved in this response. |