Experimental approaches to understanding virulence in toxoplasmosis

Toxoplasma gondii Is a widespread protozoan parasite that causes severe dis ease only in immunocompromised individuals. Equipped with excellent animal models and relatively advanced systems for genetics, T. gondii provides an excellent system for understanding pathogenesis. desistance to toxoplasmosi s is governed by rapid innate and adaptive immunity that is characterized b y a Th1 type profile of cytokines. Despite this effective response, acute i nfections can cause considerable damage and the parasite effectively establ ishes a long-term chronic infection that predisposes the host to reactivati on and provides a means of eventual transmission. This complex interaction is brought about by the differentiation of the parasite from a rapidly repl icating, lyric form (known as the tachyzoite) to a slow-growing form (known as the bradyzoite) that gives rise to chronic infection. The population st ructure of T. gondii Is remarkably clonal, consisting of just three predomi nant lineages that are geographically widespread and found in a variety of hosts including humans. Acute virulence is strongly associated with the typ e I genotype which exhibits an enhanced replication rate in vitro and highe r tissue burdens in vitro relative to non-virulent lineages. The pathology associated with acute infection appears to be due to excessive production o f acute inflammatory mediators, suggesting that disease is partly due to ov er-response of the host immune system. A combination of refined animal mode ls and newly developed genetic cools for establishing the relative contribu tion of genes to pathogenesis will enable a comprehensive analysis of the m olecular basis of virulence in toxoplasmosis.