The immune response of mice to gastric cryptosporidium infections

The immune response in stomach mucosa during the primary infection and re-infection of Cryptosporidium muris (TS03 and CB03) and C. andersoni in immunocompetent BALB/c mice was observed in this study. No significant differences in the induction of a cellular response were observed in mice infected with the two strains of C. muris. Significantly elevated migration of T-lymphocytes (more than 1000-fold), especially CD8+ T lymphocytes, to the stomach mucosa was described during primary infection. Moreover, the persisting severalfold increased level of T-lymphocytes in stomach epithelium was observed 2 months after recovery from the primary cryptosporidiosis. Very low level of IFN-{$\gamma$} production in ex vivo cultures of splenocytes was recorded during the course of the primary infection (0.5 ng/ml), whereas during reinfection the concentration of IFN-{$\gamma$} rapidly increased 22-fold (10.7 ng/ml). After infection of BALB/c mice with C. andersoni LI03, migration of T-lymphocytes and production of INF-{$\gamma$} in ex vivo splenocyte primary cultures was also observed, even though this isolate of C. andersoni does not infect Mus musculus. These results imply that the CD8+ T-lymphocytes are involved in the immune response to gastric cryptosporidiosis and could play an important role in the elimination of C. muris infection in mice

Development of protective immune response in gastric mucosa of mice infected with \kur{Cryptosporidium muris} and \kur{Cryptosporidium andersoni}

The development of immune response accountable for the ability to control Cryptosporidium muris TS03 infection was studied using immunocompetent and various types of immunodeficient mouse models. Subsequently the immune response was characterized by analysis of leukocyte infiltration and cytokine production in gastric epithelium. Moreover, the potentiality of immunocompetent mice to develop effective immune response to C. andersoni LI03 infection with consequent protection to consequent infection of the same mice with C. muris TS03 was also studied by monitoring oocysts shedding, leukocyte infiltration of the gastric mucosa and cytokine production in ex vivo cultures of splenocytes

Activation of protective cell-mediated immune response in gastric mucosa during Cryptosporidium muris infection and re-infection in immunocompetent mice

The differences between two isolates of Cryptosporidium muris (TS03 and CB03) in activation and development of cell-mediated immune response in stomach mucosa was observed during the primary infection and re-infection in immunocompetent mouse model. The development of the immune response was characterized by analysis of leukocyte infiltration into the gastric epithelium and cytokine production in ex vivo cultures of splenocytes

Babesia, Theileria, Plasmodium and Hemoglobin

The Propagation of Plasmodium spp. and Babesia/Theileria spp. vertebrate blood stages relies on the mediated acquisition of nutrients available within the host’s red blood cell (RBC). The cellular processes of uptake, trafficking and metabolic processing of host RBC proteins are thus crucial for the intraerythrocytic development of these parasites. In contrast to malarial Plasmodia, the molecular mechanisms of uptake and processing of the major RBC cytoplasmic protein hemoglobin remain widely unexplored in intraerythrocytic Babesia/Theileria species. In the paper, we thus provide an updated comparison of the intraerythrocytic stage feeding mechanisms of these two distantly related groups of parasitic Apicomplexa. As the associated metabolic pathways including proteolytic degradation and networks facilitating heme homeostasis represent attractive targets for diverse antimalarials, and alterations in these pathways underpin several mechanisms of malaria drug resistance, our ambition is to highlight some fundamental differences resulting in different implications for parasite management with the potential for novel interventions against Babesia/Theileria infections

Composition of the gut microbiota shifted in response to <i>Hymenolepis diminuta</i> infection.

<p>Principle coordinate plots of the Bray-Curtis dissimilarity metric. A) All samples (N = 219) colored by treatment group and shaped according to time period. The seven samples are intestinal mucosa samples (triangles), and the rest are from feces. B-D) Fecal microbiota over the time course of infection. Gray = control and black = <i>H</i>. <i>diminuta</i> treatment. Each rat is represented by a different symbol/color combination. P-values for PERMANOVA with rat nested in treatment group are shown, and full results are in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0182205#pone.0182205.s008" target="_blank">S1B Table</a>) Before <i>H</i>. <i>diminuta</i> infection: Day 1 to Day 30 (n = 80), C) prepatent period of <i>H</i>. <i>diminuta</i> infection: Day 38 to Day 50 (n = 32). D) patent period of <i>H</i>. <i>diminuta</i> infection: Day 51 to Day 82 (n = 80).</p

Flow cytometry boxplot panel figure—general leukocyte populations.

<p>Abundance of leukocyte populations in flow cytometric samples from rats infected with <i>Hymenolepis diminuta</i> (dark grey, n = 4) and control rats (light grey, n = 4). The error bars represent the 95% confidence intervals for the mean cell counts at each sample location for each group. The asterisks represent a significant difference in the mean cell counts at α = 0.05 level for t-tests implemented at each time point. (*): 0.01 ≤ p < 0.05, (**): 0.001< p < 0.01. [the numbers of cells are in the chart are given in 10⁴ in duodenum & ileum, colon, in case of spleen in 10⁶].</p

A benign helminth alters the host immune system and the gut microbiota in a rat model system

<div><p>Helminths and bacteria are major players in the mammalian gut ecosystem and each influences the host immune system and health. Declines in helminth prevalence and bacterial diversity appear to play a role in the dramatic rise of immune mediated inflammatory diseases (IMIDs) in western populations. Helminths are potent modulators of immune system and their reintroduction is a promising therapeutic avenue for IMIDs. However, the introduction of helminths represents a disturbance for the host and it is important to understand the impact of helminth reintroduction on the host, including the immune system and gut microbiome. We tested the impact of a benign tapeworm, <i>Hymenolepis diminuta</i>, in a rat model system. We find that <i>H</i>. <i>diminuta</i> infection results in increased interleukin 10 gene expression in the beginning of the prepatent period, consistent with induction of a type 2 immune response. We also find induction of humoral immunity during the patent period, shown here by increased IgA in feces. Further, we see an immuno-modulatory effect in the small intestine and spleen in patent period, as measured by reductions in tissue immune cells. We observed shifts in microbiota community composition during the patent period (beta-diversity) in response to <i>H</i>. <i>diminuta</i> infection. However, these compositional changes appear to be minor; they occur within families and genera common to both treatment groups. There was no change in alpha diversity. <i>Hymenolepis diminuta</i> is a promising model for helminth therapy because it establishes long-term, stable colonization in rats and modulates the immune system without causing bacterial dysbiosis. These results suggest that the goal of engineering a therapeutic helminth that can safely manipulate the mammalian immune system without disrupting the rest of the gut ecosystem is in reach.</p></div

Experiment timeline.

<p>The entire experiment included five periods during which fecal, blood and tissue samples were collected: (i) acclimatization–rats were co-housed for a month prior to the start of experiment to acclimate laboratory conditions; (ii) before infection–the fecal samples for microbial analyses and for ELISA analyses were collected; (iii) infection–we infected rats in three consecutive days to prevent negativity of some animals from experimental group; (iv) prepatent period–period from infection to adults maturation, i.e. releasing of eggs in feces, (v) patent period–adults were present in the intestine; during prepatent and patent period were collected fecal, blood and tissue samples.</p

ELISA line graph for fluctuation of IgA antibodies from feces.

<p>Mean absorbance values for rats infected with <i>Hymenolepis diminuta</i> (dark grey, n = 4) and control rats (light grey, n = 4). Other notes as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0182205#pone.0182205.g003" target="_blank">Fig 3</a>.</p

Hematology line graph panel figure for leukocytes.

<p>Abundance of leukocytes in blood samples of rats infected with <i>Hymenolepis diminuta</i> (dark grey, n = 4) and healthy, uninfected rats (light grey, n = 4). The samples were taken before infection, during the pre-patent period (after infection before establishment), and at two time points during the patent period (after the establishment of the infection). The error bars represent the 95% confidence interval of the mean cell counts for each group of rats at each time point. The asterisks represent a significant difference in the mean cell counts at α = 0.05 level for t-tests implemented at each time point. (*): 0.01 ≤ p < 0.05, (**): 0.001< p < 0.01.</p