Immunocompetent host develops mild intestinal inflammation in acute infection with Toxoplasma gondii

Abstract

Toxoplasma gondii (T. gondii) is the causative agent of toxoplasmosis, common zoonosis among vertebrates and high incidence worldwide. During the infection, the parasite needs to transpose the intestinal barrier to spread throughout the body, which may be a trigger for an inflammatory reaction. This work evaluated the inflammatory alterations of early T. gondii infection in peripheral blood cells, in the mesenteric microcirculation, and small intestinal tissue by measurement of MPO (myeloperoxidase) activity and NO (nitric oxide) level in rats. Animals were randomly assigned into control group (CG) that received saline orally and groups infected with 5,000 oocysts for 6 (G6), 12 (G12), 24 (G24), 48 (G48) and 72 hours (G72). Blood samples were collected for total and differential leukocyte count. Intravital microscopy was performed in the mesentery to evaluate rolling and adhesion of leukocytes. After euthanasia, 0.5cm of the duodenum, jejunum and ileum were collected for the determination of MPO activity, NO level and PCR to identify the parasite DNA and also the mesentery were collected to perform immunohistochemistry on frozen sections to quantify adhesion molecules ICAM-1, PECAM-1 and P-Selectin. The parasite DNA was identified in all infected groups and there was an increase in leukocytes in the peripheral blood and in expression of ICAM-1 and PECAM-1 in G6 and G12, however, the expression of P-selectin was reduced in G12. Leukocytes are in rolling process during the first 12 hours and they are adhered at 24 hours post-infection. The activity of MPO increased in the duodenum at 12 hours, and NO increased in the jejunum in G72 and ileum in G24, G48 and G72. Our study demonstrated that T. gondii initiates the infection precociously (at 6 hours) leading to a systemic activation of innate immune response resulting in mild inflammation in a less susceptible experimental model.

Intravital microscopy: Imaging host–parasite interactions in lymphoid organs

“…To our knowledge, only T. gondii has been imaged in the intestines by IVM (Coombes et al, 2013;Watanabe et al, 2018). Altogether, this IVM-based finding is fascinating in that it enabled elucidating a Trojan-horse-like mechanism of pathogen spread which might be highly relevant for other parasites also able to cross tissue barriers.…”

“…To our knowledge, only T. gondii has been imaged in the intestines by IVM (Coombes et al, ; Watanabe et al, ).…”

“…A more recent study used IVM to investigate the leucocyte's behaviour in the mesenteric circulation, as well as leucocyte–endothelium interactions following infection with T. gondii (Watanabe et al, ). The study's key findings were that haemodynamic changes already happen at the beginning of infection, in which molecules such as ICAM1, PECAM1 and P‐selectin are upregulated on the vascular endothelium.…”

Acute Toxoplasma gondii infection alters the number of neurons and the proportion of enteric glial cells in the duodenum in Wistar rats

“…We have shown that the infection can compromise the intestinal structure and innervation, even in immunocompetent individuals with no classic clinical signs of toxoplasmosis . We observed local inflammation that was possibly induced by the presence of the parasite in the organ, reflected by the presence of tissue cysts and parasitic DNA . The submucosal plexus and EGCs appear to play a primordial role in the response to infection .…”

“…[14][15][16][17][18] We observed local inflammation that was possibly induced by the presence of the parasite in the organ, reflected by the presence of tissue cysts and parasitic DNA. [19][20][21] The submucosal plexus and EGCs appear to play a primordial role in the response to infection. 17,22,23 They are able to detect inflammatory stimuli, promote alterations of their phenotype, and modulate the proliferation of other cell types.…”