Neurons are the Primary Target Cell for the Brain-Tropic Intracellular Parasite Toxoplasma gondii

Carla M. Cabral, Shraddha Tuladhar, Hans K. Dietrich, Elizabeth Nguyen, Wes R. MacDonald, Tapasya Trivedi, Asha Devineni, Anita A. Koshy

PLOS Pathogens February 19, 2016

Speaker: Shung-Hao Ku (顧聲豪)           )                        Time: 13:10~14:00, Jun 8 2016

Commentator: Dr. Wei Chen Lin (林威辰 老師)  ) Place: Room 601

Abstract:

        Toxoplasma gondii is an intracellular parasite that infects warm-blooded animals, including humans, and it chronically infects of up to 1/3 of the world’s population. In these hosts, Toxoplasma establishes a chronic infection in the brain, which the parasite accomplishes in part by injecting effector proteins, which manipulate many cellular processes, into cells it invades. In vivo studies have identified neurons as host cells for cysts but in vitro studies have found that astrocytes can also foster the development of the cysts. [1]. Here, the study uses a novel Toxoplasma-mouse model capable of marking and tracking host cells that directly interact with parasites. This system causes a parasite-triggered permanent genetic change in host cells but does not require active infection. Then, contrary to what has been shown in cell culture, Toxoplasma almost exclusively interacts with neurons, and rarely interacts with astrocytes. The major mechanism is unknown. The author hypothesized that IFN-γ might play a critical role in influencing CNS cell-parasite interactions. In the IFN-γ depletion, infection with parasites in astrocytes obviously raise. However, infection with parasites resistant to the major IFN-γ-induced immunity-related GTPases(IRGs) still causes neurons in a high ratio. Finally, the authors directly injecting parasites into the brain and to calculating the distance from neuron cell body to neuron process. Neuron : astrocyte ratios and the distance from neuron cell body to neuron process actually effect the Toxoplasma gondii primary target cell. These findings, in combination with prior work, strongly suggest that neurons are not incidentally infected, but rather they are Toxoplasma’s primary in vivo target.

Reference:

1.         Melzer TC, Cranston HJ, Weiss LM, Halonen SK. Host Cell Preference of Toxoplasma gondii Cysts inMurine Brain: A Confocal Study. J Neuroparasitology. 2010; 1. doi:10.4303/jnp/N100505