Strain hypothesis of Toxoplasma gondii infection on the outcome of human diseases

Abstract

The intracellular protozoan Toxoplasma gondii is an exceptionally successful food and waterborne parasite that infects approximately 1 billion people worldwide. Genotyping of T. gondii isolates from all continents revealed a complex population structure. Recent research supports the notion that T. gondii genotype may be associated with disease severity. Here, we (1) discuss molecular and serological approaches for designation of T. gondii strain type, (2) overview the literatures on the association of T. gondii strain type and the outcome of human disease and (3) explore possible mechanisms underlying these strain-specific pathology and severity of human toxoplasmosis. Although no final conclusions can be drawn, it is clear that virulent strains (e.g. strains containing type I or atypical alleles) are significantly more often associated with increased frequency and severity of human toxoplasmosis. The significance of highly virulent strains can cause severe diseases in immunocompetent patients and might implicated in brain disorders such as schizophrenia should led to reconsideration of toxoplasmosis. Further studies that combine parasite strain typing and human factor analysis (e.g. immune status and genetic background) are required for better understanding of human susceptibility or resistance to toxoplasmosis.

Keywords: Toxoplasma gondii; human factors; outcome of human infection; strain typing; toxoplasmosis; virulence.

Figure 1

An overview of the methods that commonly used for T. gondii strain typing and their relative advantages and limitations. PCR-RFLP, restriction fragment length polymorphism analysis; MS, microsatellite analysis; MLST, multilocus sequence typing analysis.

Figure 2

An overview of the impact of T. gondii strains on the severity of human diseases. Several effectors of T. gondii (GRA15, ROP16, ROP18 and ROP5) were identified as major factors that contributed to strain-specific differences in virulence in the mouse model. The virulent isoforms of these effectors are expressed in the type I strain, whereas avirulent isoforms are secreted by type II strain. And relatively little is known regarding T. gondii effectors of the atypical strain. Allele types are shown in subscript (i.e. ROP_I denotes the allele in type I strains). Infection with type II strains triggers Th1 immune responses which is sufficient to control parasite burden. At later time point, a balance between the pro- and anti-inflammatory responses has been reached and the infection is then mostly asymptomatic. However, serve symptoms can occur when infection is associated with human genetic risk factors. Infection with type I or atypical strains gives rise to Th2 immune response which allows the parasite to multiply and dissemination. Finally, there is an imbalance between the pro- and anti-inflammatory responses due to a shift to a Th2 type. As a consequence, infection is likely to have symptoms in patients with or without genetic susceptibility. BAL, Balance; IMBA, imbalanced; w/, with; w/o, without; ICP, immunocompromised patient; HGS, host genetic susceptibility; OT, ocular toxoplasmosis; CT, congenital toxoplasmosis; TE, toxoplasmic encephalitis.