From Entry to Early Dissemination—Toxoplasma gondii's Initial Encounter With Its Host

Abstract

Toxoplasma gondii is a zoonotic intracellular parasite, able to infect any warm-blooded animal via ingestion of infective stages, either contained in tissue cysts or oocysts released into the environment. While immune responses during infection are well-studied, there is still limited knowledge about the very early infection events in the gut tissue after infection via the oral route. Here we briefly discuss differences in host-specific responses following infection with oocyst-derived sporozoites vs. tissue cyst-derived bradyzoites. A focus is given to innate intestinal defense mechanisms and early immune cell events that precede T. gondii's dissemination in the host. We propose stem cell-derived intestinal organoids as a model to study early events of natural host-pathogen interaction. These offer several advantages such as live cell imaging and transcriptomic profiling of the earliest invasion processes. We additionally highlight the necessity of an appropriate large animal model reflecting human infection more closely than conventional infection models, to study the roles of dendritic cells and macrophages during early infection.

Early Kinetics of Intestinal Infection and Immune Responses to Two Toxoplasma gondii Strains in Pigs

“…However, in humans and pigs TLR11 and TLR12 are non-functional pseudogenes (Tosh et al, 2016). Therefore, to elicit an immune response they rely on phagocytosis of tachyzoites and subsequent recognition of T. gondii RNA and DNA via TLR7,−8, and−9 (Forsbach et al, 2008;Ishii et al, 2008;Andrade et al, 2013;Weidner et al, 2013;Betancourt et al, 2019).…”

<p>Immunoinformatics and Vaccine Development: An Overview</p>

“…For instance, Toxoplasma invades and appropriates the host cells thereby circumventing phagocytosis and then spread within their host to establish infection. 81 Vertebrates on their own are endowed with immune system robust enough to efficiently and effectively surmount the non-self-attacks. Yet the more the host's immune system elaborates, the better the organisms in their evasion of immune effector cells.…”

“…83 In eukaryotic pathogens, antigenic variation is shown by Trypanosoma brucei and Plasmodium falciparum. 81,84 Another vital cause of antigenic variation in bacteria is horizontal gene transfer (more important than point mutation) through plasmid acquisition and transduction via bacteriophages. Virulence genes are normally acquired by non-virulent organisms via these routes.…”

Avaliação funcional de Toll-Like Receptor 4 (TLR4) em células trofoblásticas humanas vilosa/extravilosa e em vilos placentários humanos de terceiro trimestre gestacional infectados por Toxoplasma gondii

“…A fase sexuada ocorre apenas no intestino delgado de alguns felídeos (BETANCOURT et al, 2019). Quando os felinos ingerem oocistos infectantes ou cistos teciduais, esporozoítos, bradizoítos ou taquizoítos são liberados na mucosa gástrica que migram para o epitélio intestinal, e penetram nos enterócitos e por esquizogonia se transformam intracelularmente em esquizontes multinucleados após 3 a 7 dias de infecção.…”

“…Um zigoto diploide irá se desenvolver dentro dos oocistos após a fertilização do gameta feminino pelo gameta masculino. Oocistos não esporulados caem na luz intestinal e são liberados para o meio ambiente juntamente com as fezes destes animais em grande quantidade, que por sua vez esporulam no meio ambiente sob condições favoráveis (MONTOYA; LIESENFELD, 2004;GANGNEUX, 2012;YAN et al, 2016;NAHOULI et al, 2017, BETANCOURT et al, 2019).…”