iTRAQ-based Quantitative Proteomics Analysis Identifies Host Pathways Modulated during Toxoplasma gondii Infection in Swine

Abstract

Toxoplasma gondii is a leading cause of foodborne illness and consumption of undercooked pig meat is a major risk factor for acquiring toxoplasmosis, which causes a substantial burden on society. Here, we used isobaric tags for relative and absolute quantification (iTRAQ) labelling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify cellular proteins and pathways altered during T. gondii infection in pigs. We also used parallel reaction monitoring-based LC-MS/MS to verify the levels of protein expression of infected spleens and mesenteric lymph nodes (MLNs). At 6 days post-infection (dpi), 156, 391, 170, 292, and 200 differentially expressed proteins (DEPs) were detected in the brain, liver, lung, MLNs and spleen, respectively. At 18 dpi, 339, 351, 483, 388, and 303 DEPs were detected in the brain, liver, lung, MLNs and spleen, respectively. Although proteins involved in immune responses were upregulated in all infected tissues, protein expression signature in infected livers was dominated by downregulation of the metabolic processes. By weighted gene co-expression network analysis, we could further show that all proteins were clustered into 25 co-expression modules and that the pink module significantly correlated with the infection status. We also identified 163 potential anti-T. gondii proteins (PATPs) and provided evidence that two PATPs (HSP70.2 and PDIA3) can reduce T. gondii burden in porcine macrophages in vitro. This comprehensive proteomics analysis reveals new facets in the pathogenesis of T. gondii infection and identifies key proteins that may contribute to the pig’s defense against this infection.

Epigenome Wide Association and Stochastic Epigenetic Mutation Analysis on Cord Blood of Preterm Birth

“…Notwithstanding, this gene has been reported by several studies to be differently methylated in preterm cord blood samples; at this time its role in PTB still remains largely unexplored. However, a recent paper reported that PLCH1 expression can be modulated during toxoplasma gondii infection [ 20 ] and this finding is interesting if we consider that congenital toxoplasmosis can be a cause of preterm birth [ 21 ]. FOXK1 gene is a transcription factor of the forkhead box family (transcription factors that play important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation, and longevity).…”

Archetypal type II and III Toxoplasma gondii oocysts induce different immune responses and clinical outcomes in experimentally infected piglets

“…Similar to humans, T. gondii infection is usually asymptomatic in pigs. As observed in previous studies, some animals may develop mild clinical signs, such as fever, apathy or lack of appetite, during the acute phase of the disease and fully recovering during the chronic phase (4,(6)(7)(8)(9). Although clinical toxoplasmosis in swine is rare, outbreaks of toxoplasmosis in pigs have been reported in China and Brazil (10,11).…”

“…Host-parasite interactions during T. gondii infection in livestock species such as pigs have not been sufficiently studied (4,(6)(7)(8)(9). Here, we examined the interaction of T. gondii and piglets as well as the potential effect of two genotypes on the development of the disease (clinical outcome, immune response and parasite dissemination) and finally the persistence of the parasite in target tissues during the chronic phase.…”

“…Infection has been reproduced by inoculating different parasitic stages (tachyzoites, tissue cysts and oocysts) through different routes and in animals of different ages, which makes it difficult to compare the results obtained (7,(32)(33)(34)(35)(36)(37)(38). Previous experimental infections in pigs highlight the importance not only of the isolate but also of the dose to which animals are exposed and the parasitic stage in question [reviewed in (4)].…”

Global proteomic profiling of multiple organs of cats (Felis catus) and proteome-transcriptome correlation during acute Toxoplasma gondii infection

“…Different technologies have been used to study the molecular attributes of T. gondii, and the molecular mechanisms associated with T. gondii infection in different hosts, including proteomics [10][11][12], transcriptomics [13][14][15], and metabolomics [16][17][18]. Over the past decade, proteomic approaches have been widely used to improve the understanding of host-pathogen interactions [19,20].…”