Rosuvastatin enhances alterations caused by Toxoplasma gondii in the duodenum of mice.

Infection by Toxoplasma gondii may compromise the intestinal histoarchitecture through the tissue reaction triggered by the parasite. Thus, this study evaluated whether treatment with rosuvastatin modifies duodenal changes caused by the chronic infection induced by cysts of T. gondii. For this, female Swiss mice were distributed into infected and treated group (ITG), infected group (IG), group treated with 40 mg/kg rosuvastatin (TG) and control group (CG). After 72 days of infection, the animals were euthanized, the duodenum was collected and processed for histopathological analysis. We observed an increase in immune cell infiltration in the IG, TG and ITG groups, with injury to the Brunner glands. The infection led to a reduction in collagen fibers and mast cells. Infected and treated animals showed an increase in collagen fibers, acidic mucin-producing goblet cells, intraepithelial lymphocytes and mast cells, in addition to the reduction of muscle, neutral mucin-producing and Paneth cells. While treatment with rosuvastatin alone led to increased muscle layer, proportion of neutral mucin-producing goblet cells, Paneth cells, and reduction of collagen fibers. These findings indicate that the infection and treatment caused changes in the homeostasis of the intestinal wall and treatment with rosuvastatin potentiated most parameters indicative of inflammation.

Challenges and perspectives in research and teaching of host pathogen interaction topics: new post-pandemic times to Brazil and other South American countries.

Here is our proposal to improve learning in biomedical sciences for graduate and undergraduate courses with a broad vision integrating disciplines such as molecular cell biology, biochemistry, and biophysics around concepts of pathogen interaction within vertebrate and invertebrate hosts. Our paradigm is based on the possibility offered by the pandemic to have remote activities that give access to students and researchers from different places in Brazil and Latin American countries to discuss science. A multidisciplinary view of host-pathogen interaction allows us to understand better the mechanisms involved in the pathology of diseases, as well as to formulate broad strategies for the diagnosis, treatment, and control of thereof. The approach to integrating heterogeneous groups in science involves the critical analysis of national scientific resource distribution, where only some have the possibilities to conduct competitive scientific research. Solid theoretical training, contact, collaboration with groups of excellence, and training within a multidisciplinary network are our proposals for a permanent platform of scientific strengthening and dissemination for Latin America. Here we will review the concept of host-pathogen interaction, the type of institutions where it is taught and researched, new trends in active teaching methodologies, and the current political context in science.

Challenges and perspectives in research and teaching of host pathogen interaction topics: new post-pandemic times to Brazil and other South American countries

Here is our proposal to improve learning in biomedical sciences for graduate and undergraduate courses with a broad vision integrating disciplines such as molecular cell biology, biochemistry, and biophysics around concepts of pathogen interaction within vertebrate and invertebrate hosts. Our paradigm is based on the possibility offered by the pandemic to have remote activities that give access to students and researchers from different places in Brazil and Latin American countries to discuss science. A multidisciplinary view of host-pathogen interaction allows us to understand better the mechanisms involved in the pathology of diseases, as well as to formulate broad strategies for the diagnosis, treatment, and control of thereof. The approach to integrating heterogeneous groups in science involves the critical analysis of national scientific resource distribution, where only some have the possibilities to conduct competitive scientific research. Solid theoretical training, contact, collaboration with groups of excellence, and training within a multidisciplinary network are our proposals for a permanent platform of scientific strengthening and dissemination for Latin America. Here we will review the concept of host-pathogen interaction, the type of institutions where it is taught and researched, new trends in active teaching methodologies, and the current political context in science.

Challenges and perspectives in research and teaching of host pathogen interaction topics: new post-pandemic times to Brazil and other South American countries

Here is our proposal to improve learning in biomedical sciences for graduate and undergraduate courses with a broad vision integrating disciplines such as molecular cell biology, biochemistry, and biophysics around concepts of pathogen interaction within vertebrate and invertebrate hosts. Our paradigm is based on the possibility offered by the pandemic to have remote activities that give access to students and researchers from different places in Brazil and Latin American countries to discuss science. A multidisciplinary view of host-pathogen interaction allows us to understand better the mechanisms involved in the pathology of diseases, as well as to formulate broad strategies for the diagnosis, treatment, and control of thereof. The approach to integrating heterogeneous groups in science involves the critical analysis of national scientific resource distribution, where only some have the possibilities to conduct competitive scientific research. Solid theoretical training, contact, collaboration with groups of excellence, and training within a multidisciplinary network are our proposals for a permanent platform of scientific strengthening and dissemination for Latin America. Here we will review the concept of host-pathogen interaction, the type of institutions where it is taught and researched, new trends in active teaching methodologies, and the current political context in science.

Moderate intestinal immunopathology after acute oral infection with Toxoplasma gondii oocysts is associated with expressive levels of serotonin.

BACKGROUND: Invasion of the intestinal mucosa by T. gondii elicits a local immune response of variable intensity. These reactions can be lethal in C57BL/6 mice. The tissue damage caused by inflammation and the functional effects depend on the host immunity, strain, and developmental form of the parasite. We investigated the effects of acute oral infection with T. gondii on histoarchitecture, enteric nervous system (ENS), and inflammatory markers in the jejunum and ileum of mice. METHODS: Female C57BL/6 mice were divided into a control group and a group orally infected with 1000 sporulated T. gondii oocysts (ME-49 strain). After 5 days, jejunum and ileum were collected and processed for analyzes (e.g., histological and histopathological examinations, ENS, cytokine dosage, myeloperoxidase, nitric oxide activity). MAIN RESULTS: In infected mice, we observed a significant increase in serotonin-immunoreactive cells (5-HT IR) in the intestinal mucosa, as well as cellular infiltrates in the lamina propria, periganglionitis, and ganglionitis in the myenteric plexus. We also noted decreased neuron density in the jejunum, increased population of enteric glial cells in the ileum, histomorphometric changes in the intestinal wall, villi, and epithelial cells, remodeling of collagen fibers, and increased myeloperoxidase activity, cytokines, and nitric oxide in the intestine. CONCLUSIONS AND INFERENCES: Acute infection of female mice with T. gondii oocysts resulted in changes in ENS and a marked increase in 5-HT. These changes are consistent with its modulatory role in the development of moderate acute inflammation. The use of this experimental model may lend itself to studies aimed at understanding the pathophysiological mechanisms of intestinal inflammation in humans involving ENS.

A New Target Organ of Leishmania (Viannia) braziliensis Chronic Infection: The Intestine.

Leishmania (Viannia) braziliensis is one of the main causes of cutaneous leishmaniasis in the Americas. This species presents genetic polymorphism that can cause destructive lesions in oral, nasal, and oropharyngeal tracts. In a previous study, the parasite caused several histopathological changes to hamster ileums. Our study evaluates immune response components, morphological changes, and effects on neurons in the ileums of hamsters infected by three different strains of L. (V.) braziliensis in two infection periods. For the experiment, we separated hamsters into four groups: a control group and three infected groups. Infected hamsters were euthanized 90- or 120-days post infection. We used three strains of L. (V.) braziliensis: the reference MHOM/BR/1975/M2903 and two strains isolated from patients who had different responses to Glucantime® treatment (MHOM/BR/2003/2314 and MHOM/BR/2000/1655). After laparotomy, ileums were collected for histological processing, biochemical analysis, and evaluation of neurons in the myenteric and submucosal plexuses of the enteric nervous system (ENS). The results demonstrated the increase of blood leukocytes after the infection. Optical microscopy analysis showed histopathological changes with inflammatory infiltrates, edemas, ganglionitis, and Leishmania amastigotes in the ileums of infected hamsters. We observed changes in the organ histoarchitecture of infected hamsters when compared to control groups, such as thicker muscular and submucosa layers, deeper and wider crypts, and taller and broader villi. The number of intraepithelial lymphocytes and TGF-ß-immunoreactive cells increased in all infected groups when compared to the control groups. Mast cells increased with longer infection periods. The infection also caused remodeling of intestinal collagen and morphometry of myenteric and submucosal plexus neurons; but this effect was dependent on infection duration. Our results show that L. (V.) braziliensis infection caused time-dependent alterations in hamster ileums. This was demonstrated by the reduction of inflammatory cells and the increase of tissue regeneration factors at 120 days of infection. The infected groups demonstrated different profiles in organ histoarchitecture, migration of immune cells, and morphometry of ENS neurons. These findings suggest that the small intestine (or at least the ileum) is a target organ for L. (V.) braziliensis infection, as the infection caused changes that were dependent on duration and strain.

Acute infection with Toxoplasma gondii oocysts preferentially activates non-neuronal cells expressing serotonin in the jejunum of rats.

The interaction of Toxoplasma gondii with the gastrointestinal tract of its host is highly regulated. Once ingested, the parasite crosses the epithelium without altering the permeability of the intestinal barrier. Nevertheless, many studies report alterations ranging from structural to functional damage in cells and tissues that make up the wall of the small and large intestine. Although the immune response to the parasite has been extensively studied, the role of serotonin (5-HT) in toxoplasmosis is poorly understood. Here we investigate the distribution of cells expressing 5-HT and its effects on cells and tissues of the jejunal wall of rats after 2, 3, or 7 days of T. gondii infection. KEY RESULTS: Our results show that transposition of the jejunal epithelium by T. gondii leads to ruptures in the basement membrane and activation of the immune system, as confirmed by the decrease in laminin immunostaining and the increase in the number of mast cells, respectively. CONCLUSIONS AND INFERENCES: We showed an increase in the number of enterochromaffin cells and mast cells expressing 5-HT in the jejunal wall. We also observed that the percentage of serotonergic mast cells increased in the total population. Thus, we can suggest that oral infection by T. gondii oocysts preferentially activates non-neuronal cells expressing 5-HT. Together, these results may explain both the changes in the extracellular matrix and the morphology of the enteric ganglia.

Infection by Leishmania (Leishmania) infantum chagasi causes intestinal changes B-1 cells dependent.

Evaluating the histopathological and morphometric changes caused by Leishmania (Leishmania) infantum chagasi infection either in the presence or absence of B-1 cells. Wild-type Balb/c and XID mice were used. Half of XID mice received B-1 cells adoptive transfer (XID + B1). Five animals from each group were infected (Balb/c I, XID I and XID + B1 I), totalizing six groups (n = 5). After 45 days of infection, the ileum was collected for histological processing and analysis. After infection, the XID animals showed an increase in the thickness of the intestinal layers, in the depth and width of the crypt and in the villi width. However, the Balb/c I group showed a reduction in almost all these parameters, whereas the villi width was increased. The villi height decreased in the infected XID animals; however, it was increased in the XID + B1 I group. Leishmania (L) infantum chagasiinfection caused a decrease in the number of Paneth cells; however, their area was increased. Finally, goblet cells and enterocytes presented different change profiles among groups. This study showed that the parasite infection causes structural and histopathological alterations in the intestine. These changes might be influenced by the absence of B-1 cells.

Toxoplasma gondii causes lipofuscinosis, collagenopathy and spleen and white pulp atrophy during the acute phase of infection.

In this study, we evaluated homeostatic and functional disorders of the spleen in mice inoculated with Toxoplasma gondii. The kinetics of megakaryocyte and leukocyte production, body and spleen mass and certain histopathological aspects were analyzed. There was increased (P < 0.05) the accumulation of lipofuscin in the red pulp of the spleen, in the periods of 30 and 60 dpi of the infection, that is, in the chronification stage of the disease and decrease of the white pulp area. In addition, we observed (from 7dpi) a quantitative and qualitative increase (P < 0.05) in the deposition of collagen fibers in the spleen of all infected mice. Since resolution of the inflammatory process resulted in pathophysiological changes, we can suggest that the T. gondii invaded and multiplied in the cells of the white and red pulps of the spleen. Although we did not find the parasite in the spleen, this hypothesis is supported by the presence of diffuse inflammatory infiltrate, which extended through the spleen parenchyma of all inoculated mice. Taken together, our results suggest that T. gondii causes severe homeostatic disorders that have altered spleen physiology, including diffuse parenchymal inflammation, lipofuscinosis in histiocytes, early aging, collagenopathy, systemic sclerosis and spleen and white pulp atrophy.

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

BACKGROUND: Toxoplasma gondii infection can occur through the ingestion of raw meat that contains tissue cysts or food that contains oocysts. Through the ingestion of oocysts, the parasite crosses the intestinal barrier, where the enteric nervous system is located. The objective was to investigate the kinetics of neuronal and glial responses during acute T. gondii infection. METHODS: We used 45 Wistar rats that were divided into a control group and infected groups that were evaluated at 6, 12, 24, 48, 72 hours, 7 days, 10 days, and 15 days after infection. The rats received 5000 sporulated oocysts of the parasite orally. To detect neurons and enteric glia cells, the myenteric and submucosal plexuses of the duodenum underwent double-labeling immunohistochemical techniques to evaluate HuC/HuD and S100, HuC/HuD and ChAT, and HuC/HuD and nNOS. KEY RESULTS: We observed a reduction of the total neuron population in the submucosal plexus 72 hours after infection. Cholinergic neurons decreased in the submucosal plexus 15 days after infection, and nitrergic neurons decreased in the myenteric plexus 72 hours after infection. A decrease in the number of glial cells was observed 7 days after infection in the submucosal plexus, and an increase in the enteric glial cell (EGC)/neuron ratio was found in both plexuses 48 hours after infection. CONCLUSIONS AND INFERENCES: We found decrease of neurons and increase in the EGC/neuron ratio in both plexuses caused by acute T. gondii infection, with major alterations 72 hours after oral infection. The number of cholinergic neurons decreased in the submucosal plexus, and the number of nitrergic neurons decreased in the myenteric plexus. A decrease in the number of enteric glial cells was observed in the submucosal plexus, and an increase in the enteric glial cell/neuron ratio was observed in both ganglionate plexuses of the duodenum.