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Role of the Toll/interleukin-1 receptor signaling pathway in host resistance and pathogenesis during infection with protozoan parasites.

Different studies have illustrated the activation of the innate immune system during infection with protozoan parasites. Experiments performed in vivo also support the notion that innate immunity has a crucial role in resistance as well as pathogenesis observed during protozoan infections such as malaria, leishmaniasis, toxoplasmosis, and trypanosomiasis. While major advances have been made in the assignment of bacterial molecules as Toll-like receptors (TLRs) agonists as well as defining the role of the Toll/interleukin-1 receptor (TIR) signaling pathway in host resistance to bacterial infection, this research area is now emerging in the field of protozoan parasites. In this review, we discuss the recent studies describing parasite molecules as TLR agonists and those studies indicating the essential role of the TIR-domain bearing molecule named myeloid differentiation factor 88 in host resistance to infection with protozoan parasites. Together, these studies support the hypothesis that the TIR signaling pathway is involved in the initial recognition of protozoan parasites by the immune system of the vertebrate host, early resistance to infection, development of acquired immunity, as well as pathology observed during acute infection with this class of pathogens.

Animals↗

Signaling of immune system cells by glycosylphosphatidylinositol (GPI) anchor and related structures derived from parasitic protozoa.

Glycosylphosphatidylinositol (GPI) anchor and glycoinositolphospholipid (GIPL) are abundant molecules present in the membrane of parasitic protozoa that are common etiologic agents of medical and veterinary diseases. Recent studies have documented the immunostimulatory/regulatory activity of protozoan-derived GPI-anchors and related structures. Among the bioactivity displayed by the protozoan-derived GPI-anchor is the ability to elicit the synthesis of pro-inflammatory cytokines as well as nitric oxide by host macrophages. In contrast, at high concentrations GIPL and lipophosphoglycan (LPG) derived from protozoan parasites suppress several functions of the host immune system. Additionally, the protozoan-derived GPI-anchor and GIPL have been shown to serve as targets for both specific B and NK-T lymphocyte responses. This information extends our knowledge about parasite molecules that stimulate/regulate the host immune system during protozoan infection. The identification of receptor(s) and signaling pathways triggered by these GPI-related glycolipids may provide new insights for the development of therapies that inhibit detrimental immune responses or potentiate beneficial immune responses observed during infection with protozoan parasites.

Animals↗

Protozoon infections and intestinal permeability.

Intestinal permeability (IP) studies using some macromolecules have been assumed to demonstrate the intactness of intestinal mucosa. The aim of the present study is to determine the changes in IP among patients with protozoan infections. Thirty nine patients with protozoan infections and ten healthy controls were enrolled in the study. Protozoa were diagnosed by Native-lugol, Richie and Trichrome staining of faeces. IP was evaluated by diethyl triamine penta acetic acid labeled with 99m Technetium (99mTc labeled DTPA) assay. The IP was found to have increased in patients with protozoan infections compared with control patients (7.20+/-5.52 vs. 4.47+/-0.65%, P=0.0017). The IP values were 9.91+/-10.05% in Giardia intestinalis group, 6.81+/-2.25% in Blastocystis hominis group, 5.78+/-2.84% in Entamoeba coli group. In comparison with the control group, the IP was significantly higher in G. intestinalis and B. hominis patients (P=0.0025, P=0.00037, respectively), but not in E. coli patients. In conclusion, the IP increases in patients with G. intestinalis and B. hominis but not with E. coli infection. This finding supports the view that IP increases during the course of protozoan infections which cause damage to the intestinal wall while non-pathogenic protozoan infections have no effect on IP. The increase in IP in patients with B. hominis brings forth the idea that B. hominis can be a pathogenic protozoan.

Adult↗

Immunity and intracellular infection: resistance to bacteria in mice infected with a protozoan.

Mice infected with the intracellular parasite Toxoplasma gondii for periods of as long as 7 months were resistant to challenge with numbers of Listeria monocytogenes and Salmonella typhimurium that were uniformly lethal to normal mice. This resistance did not appear to depend on the strain of toxoplasma employed or the route of inoculation of either toxoplasma or bacteria. Onset of immunity to listeria was demonstrable as early as 1 to 2 days after infection with toxoplasma. Resistance to toxoplasma was not demonstrable in mice immune to listeria. Interferon did not appear to be a mediator of the immunity observed in toxoplasma-infected mice.

Animals↗

Humoral and cellular immunity against Cryptosporidium infection.

Protozoans of the genus Cryptosporidium are the etiological agents of opportunistic infections mainly of the gastrointestinal tract of animals and humans. Young and elderly persons, those with concomitant infections, with AIDS, under an immunosuppressive therapy, with congenital T-cell, B-cell or other effector cell deficiencies develop persistent progressive infections of different degree of severity related to the level of immunodepression. Both humoral and cellular immunity play a role in the control of this infection, but the latter plays the major role, mainly in the intestinal mucosa. However, a natural resistance to these coccidian parasites is also involved. IgG, IgM and IgA have been detected in serum and mucosa of humans and animals with the resolution of the infection; but also high levels of these immunoglobulins have been detected in persons with AIDS with chronic cryptosporidiosis. In HIV-positive persons, CD4+ T-cells are required to prevent the establishment of the infection and IFN-gamma and CD4+ T-cells can also limit the duration and the clinical manifestations of the infection. In persons exposed to cryptosporidial infections, it has been possible to show the important role of IFN-gamma in both the innate and acquired cell mediated immunity. The severity of cryptosporidiosis has been also associated with the inability to produce IFN-gamma. An antibody therapy using bovine colostrum from cows hyperimmunised with Cryptosporidium oocysts or monoclonal antibodies against sporozoite antigens has been developed at the experimental level mainly for persons with AIDS or with other immunodeficiencies; however, these preparations of antibodies have shown only a limited degree of efficacy both in animals and humans.

Animals↗

Tumour necrosis factor alpha receptors: role in the physiopathology of protozoan parasite infections.

Tumour necrosis factor alpha (TNF alpha) is an important cytokine in immune regulation and resistance to various micro-organisms. It provides signals to the target cells through two different receptors: TNFR1 and TNFR2. The present report reviews the role of TNF receptors (TNFRs) in the immune response against protozoan parasite infections of medical interest (Toxoplasma gondii, Leishmania major, Trypanosoma cruzi, Plasmodium spp.). TNF alpha has been regarded as a modulator cytokine in host defence against protozoans infections and recent findings on experimental gene-deficient mice have showed that TNF alpha/TNFRs pathway may be beneficial for host protection during these infections.

Animals↗

Environmental contamination with protozoan parasite infective stages: biology and risk assessment.

In the present paper some aspects of the biology and various factors influencing the potential for environmental contamination with protozoan parasites infective stages implicated in water and foodborne diseases are described. The major protozoan species that affect humans are Entamoeba histolytica, Acanthamoeba sp., Neagleria sp. Giardia intestinalis, Cryptosporidium parvum, Cyclospora cayetanensis, Toxoplasma gondii, Isospora/Sarcocystis sp. Encephalitozoom intestinals and Enterocytozoon bieneuisi. These parasites exist in the environment as oocyst, cysts or spores, which are the transmissive stages in many environmental conditions, e.g. water, soil, food as well as being infective stages to subsequent generation of hosts. Global concern with parasitic contamination of our environment must influence development of better detection methods and of evaluation and risk assessment of these infections. In this paper, the biology, waterborne and foodborne transmission, as well as methods for detection and control of Cryptosporidium parvum, Giardia intestinals and Toxoplasma gondii will be described.

Animals↗

Specific IgG1 and IgG2 antibody responses of dogs to Leishmania infantum and other parasites.

Sera from dogs naturally infected with Leishmania infantum were analysed for the IgG subclass specificity of their antibody response by ELISA. Dogs infected with L. infantum produced both IgG1 and IgG2 antibodies with IgG2 being associated with asymptomatic infections and IgG1 being associated with disease (symptomatic dogs, non- or low-responsive to chemotherapy). The differential responses of IgG1 and IgG2 serum antibodies in asymptomatic and symptomatic dogs may indicate a dichotomous immune response to infection with L. infantum. To confirm this, on a broader scale, sera from dogs naturally exposed to an asymptomatic protozoan infection, Toxoplasma gondii, were also analysed as were sera from dogs exposed to the helminths, Dirofilaria immitis and Toxocara canis. Antibodies specific for T. gondii antigen detected in sera from 17 dogs were of the IgG2 subclass only. Both IgG1 and IgG2 antibodies to D. immitis and T. canis were present in the sera of naturally infected dogs but IgG1 appeared to be the predominant subclass. Furthermore, in dogs experimentally infected with T. canis, selective regulation of IgG2 and IgG1 responses was apparent since production of the two subclasses occurred at different times following infection, with IgG2 levels declining as IgG1 levels rose. Thus, the analysis of IgG subsets in parasitized dogs provides evidence of a dichotomous response to infection: IgG2 is associated with asymptomatic protozoan infections and IgG1 is associated with helminth infections and disease caused by protozoan infection.

Animals↗

Effect of dietary magnesium on the susceptibility of mice to infection by protozoan parasites of the Apicomplexa and Mastigophora phyla.

Severe magnesium deficiency protects mice against infections by Plasmodium Spp. and Babesia hylomysci which invade mature erythrocytes. By contrast severe magnesium deficiency does not protect against parasite infections by P. berghei which invades reticulocytes, Toxoplasma gondii which invades macrophages, and Trypanosoma brucei which lives free in blood. The results indicate that the infectious response depends on the severity of magnesium deficiency and on the parasite species. The decrease in red blood cell magnesium and increased oxidant stress are possible explanations for the protective effect of magnesium deficiency.

Animals↗

Polyparasitism with Schistosoma mansoni, geohelminths, and intestinal protozoa in rural Côte d'Ivoire.

Single species infections with schistosomes, geohelminths, and intestinal protozoans are common over large parts of sub-Saharan Africa, and it is expected that polyparasitism affects a considerable proportion of the population, hence posing a great toll on public health. However, few investigations have been carried out to quantify the extent of polyparasitism. Here, a detailed assessment is reported for the epidemiology of Schistosoma mansoni, geohelminths, and intestinal protozoan infections, with particular emphasis on polyparasitism among 260 community members in rural Cĵte d'Ivoire. Schistosoma mansoni, Entamoeba coli, and hookworm were the predominant species with prevalences of 71.5, 64.6, and 51.9%, respectively. Only 8 individuals displayed no infection, whereas two-thirds of the population harbored 3 or more parasites concurrently. There were a series of significant pairwise parasite co-occurrences, e.g., between S. mansoni and hookworms and between S. mansoni and E. coli. It is concluded that polyparasitism in the population studied here was very common, which is probably the case also in other areas of rural Cĵte d'Ivoire and elsewhere in sub-Saharan Africa. These findings call for integrated approaches to effectively control multiple parasitic and protozoan infections.

Adolescent↗

Prevalence and risk factors for protozoan and nematode infections among children in an Ecuadorian highland community.

In order to create a parasite prevention program for Santa Ana, Ecuador, we worked with local physicians to identify the prevalence and risk factors for intestinal parasitic infection among children. Two hundred households were randomly selected and asked to submit three stool samples from a selected child. Information from direct observation and questionnaires was used to determine environmental and behavioral risk factors for parasitic infection. Prevalence of any parasitic infection was 65.6% of the 189 children who submitted fecal samples. Parasitic infections included Entamoeba histolytica/E. dispar (46.6%), Giardia lamblia (18.5%) and Ascaris lumbricoides (20.1%). In a multivariate logistic model, risk factors (P<0.05) for E. histolytica/E. dispar included >1 month since antiparasitic treatment, not adding chlorine to drinking water, children not washing their hands before eating, and having a fewer number of electrical appliances in the home. The risk factor identified for G. lamblia was children not washing their hands before eating. Risk factors for A. lumbricoides included >6 months since antiparasitic treatment and having a fewer number of electrical appliances in the home. This study may have implications for other communities throughout the developing world.

Age Distribution↗

Intestinal parasitic infections among school children of the Dhahira Region of Oman.

OBJECTIVE: To determine the prevalence of intestinal parasitic infections among primary school children in Dhahira region of Oman. METHODS: The study took place in the Dhahira region of Oman from September 2004 to March 2005. We randomly recruited 436 students of 9-10 years of age. Their anthropometric measurements were noted. We collected the stool sample of each student and examined for different intestinal parasites. Stereoscopic microscopy and the World Health Organization's approved KATO-KATZ technique were used. RESULTS: Of the 436 students examined, 65 children (15%) were undernourished (body mass index (BMI) <14 kg/m(2)). The prevalence of intestinal parasitic infections was 38.7% (95% CI 33.2-42.2). The prevalence of protozoan infection was 36% while helminth infection was 9.4%. The prevalence of Entamoeba histolytica/Entamoeba dispar was 24%, Giardia species 10.5% and Escherichia coli 1.4%. The hookworm (Ancylostoma duodenale, Necator americanus), Ascariasis lumbricoides, Trichuris trichiura, Hymenolepiasis nana, Taenia species, Enterobius vermicularis and Strongyloides infections in our study had very low prevalence. Only 29 (6.4%) students had parasitic infection by more than one parasite. The wet zone was significantly associated to the intestinal parasitic infections [Adjusted odds ratio (OR)=3.2 (95% CI 1.9-5.2)]. CONCLUSION: Dhahira region could be classified as low prevalence and low intensity area for soil transmitted helminths infections. However, the magnitude of the protozoan infection was high. The school health program should focus on parasitic infection treatment and addressing the underlying causes of this problem.

Animals↗