Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome.

While conventional pathogenic protists have been extensively studied, there is an underappreciated constitutive protist microbiota that is an integral part of the vertebrate microbiome. The impact of these species on the host and their potential contributions to mucosal immune homeostasis remain poorly studied. Here, we show that the protozoan Tritrichomonas musculis activates the host epithelial inflammasome to induce IL-18 release. Epithelial-derived IL-18 promotes dendritic cell-driven Th1 and Th17 immunity and confers dramatic protection from mucosal bacterial infections. Along with its role as a "protistic" antibiotic, colonization with T. musculis exacerbates the development of T-cell-driven colitis and sporadic colorectal tumors. Our findings demonstrate a novel mutualistic host-protozoan interaction that increases mucosal host defenses at the cost of an increased risk of inflammatory disease.

Cytokine response of human THP-1 macrophages to Trichomonas tenax.

Trichomonas tenax is a protozoan that inhabits the oral cavity of humans, most often those with poor oral hygiene. Although T. tenax is widely considered a commensal, recent studies have suggested a pathogenic role for the protozoan in persons with periodontitis. Here we investigated the capacity of T. tenax to induce pro-inflammatory cytokine secretion in human macrophages, with the idea that elicitation of inflammation may be one mechanism by which T. tenax contributes to oral pathology. Human THP-1 cells differentiated to the macrophage phenotype (dTHP-1) were incubated with live or sonicated T. tenax at trophozoite:dTHP-1 ratios of 1:5, 1:10, and 1:20. Culture media removed from the wells after 4, 8, and 16 h of stimulation were assayed by ELISA for tumor necrosis factor alpha, interleukin-1 beta, interleukin-8, and the immunoregulatory cytokine interleukin-10. Live T. tenax trophozoites failed to induce production of any of the cytokines tested, regardless of trophozoite:dTHP-1 cell ratio or length of co-incubation. T. tenax lysates stimulated interleukin-8 synthesis, but only after 16 h of incubation at the 1:5 trophozoite:dTHP-1 cell ratio. These results suggest that pro-inflammatory cytokine synthesis by human macrophages in direct response to T. tenax contributes little to oral pathology.

Growth kinetics, antigen profiling, and proteinase activity of Egyptian Trichomonas tenax isolates derived from patients having oral infections.

The role of Trichomonas tenax as a pathogen had been clearly implicated in various pathological processes that arise outside the boundaries of the mouth. Although a relationship between the increased occurrence of this protozoan and progression of periodontal disease has been demonstrated, the ability of T. tenax in causing oral infections and the precise mechanism of tissue damage is not well known. The present study aimed to investigate different isolates of T.tenax from individuals having oral infections. Plaques and/or calculi samples were collected from 70 individuals who were diagnosed as having periodontitis and/or gingivitis, then subjected to parasitological examination and culture on modified trypticase, yeast and iron medium (TYI-S-33). Isolates successfully maintained in culture were further subjected to analysis of protein profile of lysates by Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) and analysis of proteinases by non-denaturing gelatin-SDS-PAGE. Comparison of growth kinetics of seven T. tenax isolates showed a wide variability in the growth characteristics. Protein profiles of the seven isolates revealed a total 53 bands ranged in molecular weight (MW) from 5 to 95kDa using 12% resolution gel. Also, T. tenax isolates were found to possess 19 proteinase bands ranged in MW from 14 to 66kDa. The proteolytic bands were intensified by a cysteine proteinase activator and totally disappeared by treatment with a cysteine proteinase inhibitor suggesting that the proteinases were of cysteine proteinases type. The high frequency of T. tenax detected (28.6%) along with the variability in protein profiling and proteolytic activity of the isolates supports the possible pathogenicity of T. tenax and clarifies a conclusion that different strains with possibility of variable pathogenic potential may exist.

Pulmonary trichomoniasis and Trichomonas tenax.

Pulmonary trichomoniasis is usually caused by aspirated Trichomonas tenax. Adult men with chronic purulent or necrotic pulmonary disease are usually affected. Sixty-eight patients were previously described. A Russian study demonstrated pulmonary trichomoniasis in 19 of 112 patients (17%), mostly in patients with lung cancer, lung abscess, or bronchiectasis. Rarely, pulmonary trichomoniasis may be caused by an intra-abdominal (T. hominis) or genitourinary (T. vaginalis) infection. T. tenax is usually regarded as a harmless commensal of the human mouth. Its prevalence ranges from 4% to 53% and may exceed that of vaginal infection with T. vaginalis in adult females. It is frequently found in patients with poor oral hygiene. Cultural identification is superior to microscopic examination of wet-smear, gram-stained and Papanicolaou-stained preparations. Aspirated pulmonary trichomoniasis is an opportunistic infection. Until the question of possible pathogenicity is resolved, metronidazole should be given. The underlying pulmonary disease should be vigorously treated.

Pre-existing chronic infraepithelial Trichomonas invasion with consecutive immunodepression enables progression of human immunodeficiency virus: a new concept of acquired immunodeficiency syndrome pathogenesis.

All three existing species of human trichomonads cause similar immune and histopathological host responses. The elicited crossimmunity causes interspecific competition of trichomonal infections in their typical localizations, which results in very rare simultaneous colonization of the same host by different species. This phenomenon points to the existence of a unique immune disorder or subclinical sensitization, regardless of which trichomonas species is in question. The total percentage of infestations in all three species points to the most widespread parasitosis, i.e. the immunodepression of human beings. Trichomonaemia has a very strong immunodepressive action. All the other agents, including viruses act only as opportunists.

Monoclonal antibodies against Trichomonas vaginalis.

Spleen lymphocytes obtained from mice immunized with Trichomonas vaginalis ATCC 30001 were fused with P3-X63-Ag8-653 mouse myeloma in order to produce hybridoma-secreting antibodies against T. vaginalis associated antigens. Six hybridoma cloned cell lines were established; three produced IgG1, two produced IgG2a, and one produced IgM monoclonal antibody. These six monoclonal antibodies showed binding to seven isolated strains of T. vaginalis but did not bind to Giardia lamblia. Three of those monoclonal antibodies did not bind to Tritrichomonas foetus. These anti-trichomonal monoclonal antibodies should prove to be of great value as diagnostic and research reagents.

Immunoglobulin isotype of specific antibodies in reproductive tract secretions and sera in Tritrichomonas foetus-infected heifers.

Four virgin heifers were experimentally inoculated intravaginally with 7 x 10(6) Tritrichomonas foetus, and 2 heifers served as uninfected controls. The durations of infection were 13, 20, 21, and 28 weeks, respectively. An ELISA that used whole T foetus antigen was used to detect anti-T foetus immunoglobulins (IgA, IgG1, IgG2, and IgM) in vaginal, cervical, and uterine secretions, and sera during the course of infection. The vaginal and cervical antibody responses were characterized by significantly increased T foetus-specific IgA and IgG1 at 7 to 9 weeks of infection, whereas uterine IgA and IgG1 responses peaked at 10 to 12 weeks. The antibody response in serum was predominantly of the IgG1 and IgG2 subclasses. In all reproductive tract regions, IgA persisted at least until the time of T foetus clearance, and usually longer. The next most persistent isotype was IgG1, lasting longest in the vagina, then cervix, and for the shortest time in the uterus. In local secretions, IgG2 was seen only transiently, increasing at weeks 13 to 15 in the vagina, and at weeks 10 to 12 in the cervix. Little IgM, relative to that present before infection, was detected in any secretion or serum, although cervical secretions had the greatest amount. Eight to 12 weeks after clearance, the 4 experimental heifers were inoculated intravaginally with 1 x 10(5) T foetus; transient infections (2 to 3 weeks' duration) were established in only 2 of 4 heifers, as determined by culturing of reproductive tract secretions.(ABSTRACT TRUNCATED AT 250 WORDS)

Challenge infection as a means of determining the rate of disease resistant Trichomonas gallinae-free birds in a population.

Trichomonas gallinae-free pigeons and mourning doves were infected with the Jones' Barn strain of T. gallinae to determine the rate of disease resistant T. gallinae-free birds in each population. Although all birds became infected 88% of the pigeons were resistant to trichomoniasis while 82% of the mourning doves were resistant. It was concluded that these birds had been previously infected and spontaneously lost their trichomonad fauna while retaining their resistance to fatal infection.

[Physicochemical and biological properties of an allergen from Trichomonas vaginalis]. / Fiziko-khimicheskie i biologicheskie svoistva allergena iz Trichomonas vaginalis.

The chemical and biological characterization of the preparation, found to be strictly specific, is presented. The allergen is nontoxic and has sensitizing properties. The active principle of the preparation is protein.

[The induction and disappearance of complement-fixing antibodies in the blood serum of experimental animals under the antigenic action of Trichomonas vaginalis, T. hominis and T. tenax]. / Vozniknovenie i ischeznovenie komplementsviazyvaiushchikh antitel v syvorotke krovi podopytnykh zhivotnykh pod deistviem antigenov Trichomonas vaginalis, T. hominis i T. tenax.

For studying the dynamics of induction and disappearing of complement-fixing antibodies (CFA) specific to Trichomonas vaginalis, T. hominis and T. tenax we have immunized rabbits intravenously with live individuals of the protozoa as well as intravenously, intramuscularly and subcutaneously with individuals killed at 56 degrees C. Each method of immunization was carried out by 5 inoculations with intervals of 10 days. For carrying out quantitative complement fixation we have taken blood from the ear vein of all immunized rabbits immediately before the immunization and also after it, each 10th day during one year. The dynamics of rising and lowering of titres depended on the species of trichomonads and on the method of immunization. The antigens of T. vaginalis and T. hominis induced CFA in much higher titres as antigens of T. tenax. Titres of CFA specific for all three species of above-mentioned trichomonads rose most rapidly and to the highest level when the immunization of rabbits was carried out intravenously with live individuals of protozoa. Normalization of the titres of CFA has taken place during one year at least.