Memórias do Instituto Oswaldo Cruz Fundação Oswaldo Cruz, Fiocruz ISSN: 1678-8060 EISSN: 1678-8060 Vol. 104, Num. 2, 2009, pp. 221-233

Memórias do Instituto Oswaldo Cruz, Vol. 104, No. 2, March, 2009, pp. 221-233

Small intestinal inflammation following oral infection with Toxoplasma gondii does not occur exclusively in C57BL/6 mice: review of 70 reports from the literature

Maximilian Schreiner; Oliver Liesenfeld⁺

Institute for Microbiology and Hygiene, Charité Medical School Berlin, Campus Benjamin Franklin, Hindenburgdamm 27, 12203 Berlin, Germany
+ Corresponding author: oliver.liesenfeld@charite.de

Received 10 October 2008
Accepted 2 February 2009

Code Number: oc09038

ABSTRACT

Small intestinal immunopathology following oral infection with tissue cysts of Toxoplasma gondii has been described in C57BL/6 mice. Seven days after infection, mice develop severe small intestinal necrosis and succumb to infection. The immunopathology is mediated by local overproduction of Th1-type cytokines, a so-called "cytokine storm". The immunopathogenesis of this pathology resembles that of inflammatory bowel disease in humans, i.e., Crohn's disease. In this review, we show that the development of intestinal pathology following oral ingestion of T. gondii is not limited to C57BL/6 mice, but frequently occurs in nature. Using a Pubmed search, we identified 70 publications that report the development of gastrointestinal inflammation following infection with T. gondii in 63 animal species. Of these publications, 53 reports are on accidental ingestion of T. gondii in 49 different animal species and 17 reports are on experimental infections in 19 different animal species. Thus, oral infection with T. gondii appears to cause immunopathology in a large number of animal species in addition to mice. This manuscript reviews the common features of small intestinal immunopathology in the animal kingdom and speculates on consequences of this immunopathology for humankind.

Key words:Toxoplasma gondii - gastrointestinal tract - inflammation - necrosis - animal

Within eight days of peroral infection with Toxoplasma (T.) gondii, susceptible C57BL/6 mice develop severe ileal inflammation resulting in necroses of mucosal villi and complete tissue destruction. Ileitis is caused by a Th1-type immunopathology and is characterized by a CD4⁺ T cell-mediated increase in pro-inflammatory mediators, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α and nitric oxide (NO) (Liesenfeld et al. 1996, 1998). Activation of IFN-γ and TNF-α are initiated by production of IL-12 and IL-18 (Vossenkaemper et al. 2004). IL-10 and TGF-β have been identified as counter-regulatory cytokines in the inflammatory cascade (Suzuki et al. 2000, Buzoni-Gatel et al. 2001). Recently, we have shown that the ileal bacterial flora, i.e., LPS derived from Escherichia coli and Bacteroides/Prevotella spp., contributes to the immunopathology (Heimesaat et al. 2006, 2007). Thus, T. gondii-induced ileal immunopathology resembles a large number of inflammatory mechanisms that operate during the acute phases of human inflammatory bowel diseases (IBD) (Liesenfeld 2002, McGovern & Powrie 2007). IBD are characterized by chronic intestinal inflammation with acute episodes (Basset & Holton 2002, Podolsky 2002). Ulcerative colitis is restricted to the colon, whereas Crohn's disease more frequently affects the small intestines, including the terminal ileum. In this article, we review current knowledge on the development of intestinal pathology following oral ingestion of Toxoplasma in different hosts throughout the animal kingdom and discuss consequences for intestinal pathology in humans.

MATERIALS AND METHODS

Two separate PubMed searches were conducted on June 1, 2008 using the following search terms: (1) (Toxoplasma OR toxoplasmosis) AND (gastrointestinal OR intestinal OR intestine OR enteritis OR ileitis OR gut OR bowel); (2) (disseminated OR acute OR systemic) AND toxoplasmosis. We excluded the following articles: articles about infections in humans, mice, or genetically modified organisms; articles involving experimental treatment of animals; articles without descriptions of inflammation or necrosis in at least one of the following organs: gastrointestinal tract, mesenteric lymph nodes or liver; and articles describing merely isolation of T. gondii out of one of the above mentioned organs without noting inflammatory changes or necrosis.

The search retrieved 2,654 articles published between 1960-May 2008. Using the exclusion criteria, 70 articles remained and these were included in the analysis. Articles about experimental infections and observations were analyzed separately. The animal species identified in the articles were then grouped according to their taxonomic classes. Lesions were analyzed for the following organ systems: small intestines, other gastrointestinal tract locations, mesenteric lymph nodes and liver. Characteristics of lesions were further separated to distinguish between necrosis and inflammatory changes without necrosis.

RESULTS AND DISCUSSION

The Pubmed-based search revealed 70 publications on inflammatory changes in the gastrointestinal tract caused by infection with T. gondii. These publications were subdivided into observational reports and experimental infections. Table Ia, b, c, d, e, f provides an overview of all observational reports on gastrointestinal inflammation caused by T. gondii infection. There were 66 publications that reported the development of inflammatory changes in the gastrointestinal tract. Animals affected belonged to two classes (Mammalia and Aves) and 51 different species. Among the latter, inflammatory changes were most frequently reported in the orders carnivora and primates. Of all gastrointestinal organs reported to be affected, the liver (93.9% of cases) and small intestines (57.6%) were most frequently affected. Additional sites affected with less frequency were the stomach, large intestines and mesenteric lymph nodes. The parasite could be detected in a large number of these studies. Interestingly, the suborder Feliformia, the definite host for T. gondii, was also reported to develop intestinal pathology. Domestic cats, cheetahs, Pallas cats, meerkats and lions were the species reported from that suborder. Gastrointestinal pathology, independent of the species, was characterized by small intestinal necrosis with loss of the physiological villus architecture. Since these publications were observational reports, often from zoos, no information is available regarding source of infection (tissue vs. oocyst), strain or dose of infection.

Table II, b, c, d summarizes results from 20 publications on experimental infections. As in observational studies shown above, these experiments include infections in aves and mammals. In most cases, oocysts were fed orally to animals, doses ranged from 10¹ to 10⁵ oocysts and type II and III strains were used in most cases. The small intestines (95%) and liver (85%) were the organs affected with highest frequency. In most cases, small intestinal pathology was characterized by a complete loss of the villous architecture and was similar to the pathology described in observational studies discussed above.

Since pathological changes were also similar to changes observed following experimental infection of mice with tissue cysts, the pattern observed appears to be a common feature of oral infection with T. gondii. In mice, the small but not the large intestines show formation of oedema between the epithelial layer and the lamina propria, secretion of fluid from the epithelial layer into the gut lumen, mild desquamation of epithelial cells and moderate to severe necrosis. Pathological changes are most prominent in the distal part of the ileum, but the duodenum and jejunum are usually not affected. In the liver, foci of inflammation can be observed around vessels and in the parenchyma. Intracellular parasites can be detected in large numbers in the lamina propria of the ileum; parasite numbers in the liver are smaller. Intestinal pathology may lead to death in susceptible mice and other animals. The publications reviewed here suggest that the strain of Toxoplasma, the infectious inoculum and the host genetics may impact the development of intestinal pathology. It remains to be investigated whether humans also develop intestinal pathology after oral infection. Intestinal pathology has not been reported thus far, however, the parasite was detectable in AIDS-patients with reactivated disease, intestinal pathology and diarrhoea (Liesenfeld 1999). One reason for the lack of intestinal pathology in humans may be due to the dose required for the development of pathology. In animals, an inoculum of > 10² oocysts and 40-100 tissue cysts (ME49 strain) are required to induce intestinal pathology. Consumption of raw and undercooked meat or ingestion of contaminated environmental sources (i.e., water) may not harbour sufficient numbers of parasites to induce pathology. In this regard, it will be of interest to investigate whether oral infection with T. gondii is associated with IBD in humans. It is tempting to speculate whether the strong local and/or systemic immune response during the acute or latent phase of the infection may contribute to an imbalance in the homeostasis of mucosal immune responses in humans with IBD. As a first step, the prevalence of antibodies against T. gondii could be determined in patients with IBD compared to well-selected control populations; a slightly but significantly higher seropositivity rate (based on Sabin-Feldman dye test results) has been observed previously in a small cohort of Crohn's patients over the age of 40 in Israel (Rattan et al. 1986). Results of studies that include larger patient numbers should be especially interesting since an association of T. gondii infection (based on the presence of IgG antibodies) with psychiatric disorders has been suggested (Yolken & Torrey 2008).

In conclusion, development of small intestinal pathology following oral infection with T. gondii is not uncommon in the animal kingdom and the association of infection with T. gondii and gastrointestinal pathologies, including IBD in humans, deserves further investigation.

REFERENCES

• Adkesson MJ, Gorman ME, Hsiao V, Whittington JK, Langan JN 2007. Toxoplasma gondii inclusions in peripheral blood leukocytes of a red-necked wallaby (Macropus rufogriseus). Vet Clin Pathol 36: 97-100.
• Anderson DC, McClure HM 1982. Acute disseminated fatal toxoplasmosis in a squirrel monkey. J Am Vet Med Assoc 181: 1363-1366.
• Baba AI, Rotaru O 1983. Morphopathological findings in dog's acute toxoplasmosis. Morphol Embryol (Bucur) 29: 35-37.
• Bangari DS, Mouser P, Miller MA, Stevenson GW, Vemulapalli R, Thacker HL 2007. Toxoplasmosis in a woodchuck (Marmota monax) and two American red squirrels (Tamiasciurus hudsonicus). J Vet Diagn Invest 19: 705-709.
• Barrows M 2006. Toxoplasmosis in a colony of sugar gliders (Petaurus breviceps). Vet Clin North Am Exot Anim Pract 9: 617-623.
• Basset C, Holton J 2002. Inflammatory bowel disease: is the intestine a Trojan horse? Sci Prog 85: 33-56.
• Basso W, Edelhofer R, Zenker W, Möstl K, Kübber-Heiss A, Prosl H 2005. Toxoplasmosis in Pallas' cats (Otocolobus manul) raised in captivity. Parasitology 130: 293-299.
• Basso W, Venturini MC, Moré G, Quiroga A, Bacigalupe D, Unzaga JM, Larsen A, Laplace R, Venturini L 2007. Toxoplasmosis in captive Bennett's wallabies (Macropus rufogriseus) in Argentina. Vet Parasitol 144: 157-161.
• Benirschke K, Richart R 1960. Spontaneous acute toxoplasmosis in a marmoset monkey. Am J Trop Med Hyg 9: 269-273.
• Bettiol SS, Obendorf DL, Nowarkowski M, Goldsmid JM 2000. Pathology of experimental toxoplasmosis in Eastern barred bandicoots in Tasmania. J Wildl Dis 36: 141-144.
• Burns R, Williams ES, O'Toole D, Dubey JP 2003. Toxoplasma gondii infections in captive black-footed ferrets (Mustela nigripes), 1992-1998: clinical signs, serology, pathology and prevention. J Wildl Dis 39: 787-797.
• Buzoni-Gatel D, Debbabi H, Mennechet FJ, Martin V, Lepage AC, Schwartzman JD, Kasper LH 2001. Murine ileitis after intracellular parasite infection is controlled by TGF-beta-producing intraepithelial lymphocytes. Gastroenterology 120: 914-924.
• Canfield PJ, Hartley WJ, Dubey JP 1990. Lesions of toxoplasmosis in Australian marsupials. J Comp Pathol 103: 159-167.
• Cunningham AA, Buxton D, Thomson KM 1992. An epidemic of toxoplasmosis in a captive colony of squirrel monkeys (Saimiri sciureus). J Comp Pathol 107: 207-219.
• Dietz HH, Henriksen P, Bille-Hansen V, Henriksen SA 1997. Toxoplasmosis in a colony of New World monkeys. Vet Parasitol 68: 299-304.
• Dubey JP 1983. Distribution of cysts and tachyzoites in calves and pregnant cows inoculated with Toxoplasma gondii oocysts. Vet Parasitol 13: 199-211.
• Dubey JP 1989. Lesions in goats fed Toxoplasma gondii oocysts. Vet Parasitol 32: 133-144.
• Dubey JP, Brown CA, Carpenter JL, Moore JJ 1992. Fatal toxoplasmosis in domestic rabbits in the USA. Vet Parasitol 44: 305-309.
• Dubey JP, Carpenter JL 1993. Histologically confirmed clinical toxoplasmosis in cats: 100 cases (1952-1990). J Am Vet Med Assoc 203: 1556-1566.
• Dubey JP, Garner MW, Willette MM, Batey KL, Gardiner CH 2001. Disseminated toxoplasmosis in magpie geese (Anseranas semipalmata) with large numbers of tissue cysts in livers. J Parasitol 87: 219-223.
• Dubey JP, Gendron-Fitzpatrick AP, Lenhard AL, Bowman D 1988. Fatal toxoplasmosis and enteroepithelial stages of Toxoplasma gondii in a Pallas cat (Felis manul). J Protozool 35: 528-530.
• Dubey JP, Goodwin MA, Ruff MD, Kwok OC, Shen SK, Wilkins GC, Thulliez P 1994a. Experimental toxoplasmosis in Japanese quail. J Vet Diagn Invest 6: 216-221.
• Dubey JP, Hamir AN 2002. Experimental toxoplasmosis in budgerigars (Melopsittacus undulatus). J Parasitol 88: 514-519.
• Dubey JP, Hamir AN, Rupprecht CE 1990a. Acute disseminated toxoplasmosis in a red fox (Vulpes vulpes). J Wildl Dis 26: 286-290.
• Dubey JP, Hodgin EC, Hamir AN 2006. Acute fatal toxoplasmosis in squirrels (Sciurus carolensis) with bradyzoites in visceral tissues. J Parasitol 92: 658-659.
• Dubey JP, Johnstone I, Menrath VH, Topper MJ 1989. Congenital toxoplasmosis in Abyssinian cats. Vet Parasitol 32: 261-264.
• Dubey JP, Kramer LW, Weisbrode SE 1985. Acute death associated with Toxoplasma gondii in ring-tailed lemurs. J Am Vet Med Assoc 187: 1272-1273.
• Dubey JP, Lin TL 1994. Acute toxoplasmosis in a gray fox (Urocyon cinereoargenteus). Vet Parasitol 51: 321-325.
• Dubey JP, Murrell KD, Fayer R 1984. Persistence of encysted Toxoplasma gondii in tissues of pigs fed oocysts. Am J Vet Res 45: 1941-1943.
• Dubey JP, Pas A 2008. Toxoplasma gondii infection in Blanford's fox (Vulpes cana). Vet Parasitol 153: 147-151.
• Dubey JP, Ruff MD, Kwok OC, Shen SK, Wilkins GC, Thulliez P 1993. Experimental toxoplasmosis in bobwhite quail (Colinus virginianus). J Parasitol 79: 935-939.
• Dubey JP, Ruff MD, Wilkins GC, Shen SK, Kwok OC 1994b. Experimental toxoplasmosis in pheasants (Phasianus colchicus). J Wildl Dis 30: 40-45.
• Dubey JP, Thorne ET, Williams ES 1982. Induced toxoplasmosis in pronghorns and mule deer. J Am Vet Med Assoc 181: 1263-1267.
• Dubey JP, Tocidlowski ME, Abbitt B, Llizo SY 2002. Acute visceral toxoplasmosis in captive dik-dik (Madoqua guentheri smithi). J Parasitol 88: 638-641.
• Dubey JP, Weisbrode SE, Sharma SP, Al-Khalidi NW, Zimmerman JL, Gaafar SM 1979. Porcine toxoplasmosis in Indiana. J Am Vet Med Assoc 174: 604-609.
• Dubey JP, Zajac A, Osofsky SA, Tobias L 1990b. Acute primary toxoplasmic hepatitis in an adult cat shedding Toxoplasma gondii oocysts. J Am Vet Med Assoc 197: 1616-1618.
• Favoreto-Júnior S, Ferro EA, Clemente D, Silva DA, Mineo JR 1998. Experimental infection of Calomys callosus (Rodentia, Cricetidae) by Toxoplasma gondii. Mem Inst Oswaldo Cruz 93: 103-107.
• Forzán MJ, Frasca S 2004. Systemic toxoplasmosis in a five-month-old beaver, (Castor canadensis). J Zoo Wildl Med 35: 113-115.
• Furuta T, Une Y, Omura M, Matsutani N, Nomura Y, Kikuchi T, Hattori S, Yoshikawa Y 2001. Horizontal transmission of Toxoplasma gondii in squirrel monkeys (Saimiri sciureus). Exp Anim 50: 299-306.
• Gustafsson K, Uggla A, Järplid B 1997. Toxoplasma gondii infection in the mountain hare (Lepus timidus) and domestic rabbit (Oryctolagus cuniculus). I. Pathology. J Comp Pathol 117: 351-360.
• Hansen HJ, Huldt G, Thafvelin B 1977. On porcine toxoplasmosis in Sweden. Nord Vet Med 29: 381-385.
• Hartley WJ, Dubey JP, Spielman DS 1990. Fatal toxoplasmosis in koalas (Phascolarctos cinereus). J Parasitol 76: 271-272.
• Heimesaat MM, Bereswill S, Fischer A, Fuchs D, Struck D, Niebergall J, Jahn HK, Dunay IR, Moter A, Gescher DM, Schumann RR, Göbel UB, Liesenfeld O 2006. Gram-negative bacteria aggravate murine small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii. J Immunol 177: 8785-8795.
• Heimesaat MM, Fischer A, Jahn HK, Niebergall J, Freudenberg M, Blaut M, Liesenfeld O, Schumann RR, Göbel UB, Bereswill S 2007. Exacerbation of murine ileitis by Toll-like receptor 4 mediated sensing of lipopolysaccharide from commensal Escherichia coli. Gut 56: 941-948.
• Howerth EW, Rodenroth N 1985. Fatal systemic toxoplasmosis in a wild turkey. J Wildl Dis 21: 446-449.
• Inoue M 1997. Acute toxoplasmosis in squirrel monkeys. J Vet Med Sci 59: 593-595.
• Jolly RD 1969. Toxoplasmosis in piglets. N Z Vet J 17: 87-89.
• Juan-Sallés C, Prats N, López S, Domingo M, Marco AJ, Morán JF 1997. Epizootic disseminated toxoplasmosis in captive slender-tailed meerkats (Suricata suricatta). Vet Pathol 34: 1-7.
• Juan-Sallés C, Prats N, Marco AJ, Ramos-Vara JA, Borrás D, Fernández J 1998. Fatal acute toxoplasmosis in three golden lion tamarins (Leontopithecus rosalia). J Zoo Wildl Med 29: 55-60.
• Kenny DE, Lappin MR, Knightly F, Baler J, Brewer M, Getzy DM 2002. Toxoplasmosis in Pallas' cats (Otocolobus felis manul) at the Denver Zoological Gardens. J Zoo Wildl Med 33: 131-138.
• Kottwitz JJ, Preziosi DE, Miller MA, Ramos-Vara JA, Maggs DJ, Bonagura JD 2004. Heart failure caused by toxoplasmosis in a fennec fox (Fennecus zerda). J Am Anim Hosp Assoc 40: 501-507.
• Last RD, Suzuki Y, Manning T, Lindsay D, Galipeau L, Whitbread TJ 2004. A case of fatal systemic toxoplasmosis in a cat being treated with cyclosporin A for feline atopy. Vet Dermatol 15: 94-198.
• Liesenfeld O 1999. Immune responses to Toxoplasma gondii in the gut. Immunobiology 201: 229-239.
• Liesenfeld O 2002. Oral infection of C57BL/6 mice with Toxoplasma gondii: a new model of inflammatory bowel disease? J Infect Dis 185 (Suppl. 1): S96-101.
• Liesenfeld O, Kang H, Park D, Nguyen TA, Parkhe CV, Watanabe H, Abo T, Sher A, Remington JS, Suzuki Y 1998. TNF-alpha, nitric oxide and IFN-gamma are all critical for development of necrosis in the small intestine and early mortality in genetically susceptible mice infected perorally with Toxoplasma gondii. Parasite Immunol 21: 365-376.
• Liesenfeld O, Kosek J, Remington JS, Suzuki Y 1996. Association of CD4+ T cell-dependent, interferon-gamma-mediated necrosis of the small intestine with genetic susceptibility of mice to peroral infection with Toxoplasma gondii. J Exp Med 184: 597-607.
• Lloyd C, Stidworthy MF 2007. Acute disseminated toxoplasmosis in a juvenile cheetah (Acinonyx jubatus). J Zoo Wildl Med 38: 475-478.
• Martínez-Carrasco C, Bernabé A, Ortiz JM, Alonso FD 2005. Experimental toxoplasmosis in red-legged partridges (Alectoris rufa) fed Toxoplasma gondii oocysts. Vet Parasitol 130: 55-60.
• McGovern D, Powrie F 2007. The IL23 axis plays a key role in the pathogenesis of IBD. Gut 56: 1333-1336.
• McOrist S, Smales L 1986. Morbidity and mortality of free-living and captive echidnas, Tachyglossus aculeatus (Shaw), in Australia. J Wildl Dis 22: 375-380.
• Mehdi NA, Kazacos KR, Carlton WW 1983. Fatal disseminated toxoplasmosis in a goat. J Am Vet Med Assoc 183: 115-117.
• Migaki G, Allen JF, Casey HW 1977. Toxoplasmosis in a California sea lion (Zalophus californianus). Am J Vet Res 38: 135-136.
• Migaki G, Sawa TR, Dubey JP 1990. Fatal disseminated toxoplasmosis in a spinner dolphin (Stenella longirostris). Vet Pathol 27: 463-464.
• Mikaelian I, Dubey JP, Martineau D 1997. Severe hepatitis resulting from toxoplasmosis in a barred owl (Strix varia) from Québec, Canada. Avian Dis 41: 738-740.
• Morales JA, Peña MA, Dubey JP 1996. Disseminated toxoplasmosis in a captive porcupine (Coendou mexicanus) from Costa Rica. J Parasitol 82: 185-186.
• Ocholi RA, Kalejaiye JO, Okewole PA 1989. Acute disseminated toxoplasmosis in two captive lions (Panthera leo) in Nigeria. Vet Rec 124: 515-516.
• Oksanen A, Gustafsson K, Lundén A, Dubey JP, Thulliez P, Uggla A 1996. Experimental Toxoplasma gondii infection leading to fatal enteritis in reindeer (Rangifer tarandus). J Parasitol 82: 843-845.
• Pertz C, Dubielzig RR, Lindsay DS 1997. Fatal Toxoplasma gondii infection in golden lion tamarins (Leontopithecus rosalia rosalia). J Zoo Wildl Med 28: 491-493.
• Pimenta AL, Piza ET, Cardoso Júnior RB, Dubey JP 1993. Visceral toxoplasmosis in dogs from Brazil. Vet Parasitol 45: 323-326.
• Podolsky DK 2002. Inflammatory bowel disease. N Engl J Med 347: 417-429.
• Rattan J, Hallak A, Shvartzman H, Felner S, Gilat T 1986. Sabin-Feldman dye test in ulcerative colitis and Crohn's disease. Dis Colon Rectum 29: 402-404.
• Reddacliff GL, Hartley WJ, Dubey JP, Cooper DW 1993. Pathology of experimentally-induced, acute toxoplasmosis in macropods. Aust Vet J 70: 4-6.
• Reed WM, Turek JJ 1985. Concurrent distemper and disseminated toxoplasmosis in a red fox. J Am Vet Med Assoc 187: 1264-1265.
• Resendes AR, Almería S, Dubey JP, Obón E, Juan-Sallés C, Degollada E, Alegre F, Cabezón O, Pont S, Domingo M 2002. Disseminated toxoplasmosis in a Mediterranean pregnant Risso's dolphin (Grampus griseus) with transplacental fetal infection. J Parasitol 88: 1029-1032.
• Sedlák K, Literák I, Faldyna M, Toman M, Benák J 2000. Fatal toxoplasmosis in brown hares (Lepus europaeus): possible reasons of their high susceptibility to the infection. Vet Parasitol 93: 13-28.
• Seibold HR, Wolf RH 1971. Toxoplasmosis in Aotus trivirgatus and Callicebus moloch. Lab Anim Sci 21: 118-120.
• Spencer JA, Joiner KS, Hilton CD, Dubey JP, Toivio-Kinnucan M, Minc JK, Blagburn BL 2004. Disseminated toxoplasmosis in a captive ring-tailed lemur (Lemur catta). J Parasitol 90: 904-906.
• Sørensen KK, Mørk T, Sigurdardóttir OG, Asbakk K, Akerstedt J, Bergsjø B, Fuglei E 2005. Acute toxoplasmosis in three wild arctic foxes (Alopex lagopus) from Svalbard, one with co-infections of Salmonella Enteritidis PT1 and Yersinia pseudotuberculosis serotype 2b. Res Vet Sci 78: 161-167.
• Suzuki Y, Sher A, Yap G, Park D, Neyer LE, Liesenfeld O, Fort M, Kang H, Gufwoli E 2000. IL-10 is required for prevention of necrosis in the small intestine and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice following peroral infection with Toxoplasma gondii. J Immunol 164: 5375-5382.
• Túry E, Messias AC, Belák K, Gimeno EJ 2001. Acute disseminated toxoplasmosis in a captive three-toed sloth (Bradypus tridactylus). J Comp Pathol 125: 228-231.
• Vossenkaemper A, Struck D, Alvarado-Esquivel C, Went T, Takeda K, Akira S, Pfeffer K, Alber G, Lochner M, Förster I, Liesenfeld O 2004. Both IL-12 and IL-18 contribute to small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii, but IL-12 is dominant over IL-18 in parasite control. Eur J Immunol 34: 3197-3207.
• Werner H, Janitschke K, Köhler H 1969. Über Beobachtungen an Marmoset-Affen Saguinus (Oedipomidas) oedipus nach oraler und intraperitonealer Infektion mit verschiedenen zystenbildenden Toxoplasma-Stämmen unterschiedlicher Virulenz. I. Mitteilung: Klinische, pathologisch-anatomische, histologische und parasitologische Befunde. Zentralbl Bakteriol [Orig] 209: 553-569.
• Work TM, Massey JG, Lindsay D, Dubey JP 2002. Toxoplasmosis in three species of native and introduced Hawaiian birds. J Parasitol 88: 1040-1042.
• Yolken RH, Torrey EF 2008. Are some cases of psychosis caused by microbial agents? A review of the evidence. Mol Psychiatry 13: 470-479.

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