Effects of Toxoplasma gondii genotype and absence of host MAL/Myd88 on the temporal regulation of gene expression in infected microglial cells.

The majority of strains of Toxoplasma gondii belong to three distinct clonal lines known as types I, II, and III. The outcome of the immune response to infection is influenced by the parasite strain type. The goal of this study was to examine differences in the kinetics of gene expression in microglial cells infected with types I, II, or III of T. gondii. In addition, a requirement for the integrity of host Toll-like receptor (TLR) signaling in parasite-mediated changes in gene expression was evaluated. Wild type murine microglial cells infected with T. gondii displayed different kinetic patterns of pro-inflammatory cytokine expression that were dependent on the parasite strain type. In general, types II and III elicited higher sustained responses compared to type I which induced fluctuating patterns of cytokine gene expression. Contrary to this, differences in the induction of anti-apoptotic gene expression were minimal among the different type strains throughout infection. Experiments with cells lacking the TLR adaptor molecules MAL and Myd88 showed a dependency on these factors for the pro-inflammatory response but not the anti-apoptotic response. The results show that the outcome of gene expression in T. gondii-infected microglial cells is dependent on the parasite strain type in a time-dependent manner and is selective to particular subsets of genes. The induction of an anti-apoptotic response by T. gondii infection in the absence of TLR signaling reflects a complex level of modulation of host functions by the parasite.