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Gut commensal bacteria exacerbate toxoplasmosis associated with TgSheepCHn5 (ToxoDB#2) and TgRedpandaCHn1 (ToxoDB#20) through Th1 immune response

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Abstract

Oral infection of mice with several strains of Toxoplasma gondii results in intestinal pathological lesions, which contributes to the invasion of this parasite. However, the exact mechanism is unclear, and only a few strains have been explored. Here, T. gondii TgSheepCHn5 and TgRedpandaCHn1 strains from sheep and red panda were evaluated. The TgSheepCHn5 and TgRedpandaCHn1 strains induced intestinal lesions, loss of Paneth cells, and gut commensal bacteria dysbiosis in Swiss Webster mice. The lesions and loss of Paneth cells were dependent on IFN-γ and gut commensal bacteria during T. gondii infection. Deleting IFN-γ or gut commensal bacteria suppressed the Th1 immune response, alleviated the lesions and parasite loading, and upregulated the number of Paneth cells. Loss of IFN-γ production accelerated mice death, whereas the deletion of gut commensal bacteria enhanced the survival time of the host. The Th1 cell immune responses have positive and negative effects on toxoplasmosis, resistance to T. gondii infection, and acceleration intestine lesions. Adjustment of Th1 cell responses and gut commensal bacteria may be effective treatments for toxoplasmosis.

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Data availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request. The TgSheepCHn5, TgRedpandaCHn1, and VEG strains were cryopreserved and available for further analysis.

References

  • Araujo A, Safronova A, Burger E, López-Yglesias A, Giri S, Camanzo ET, Martin AT, Grivennikov S, Yarovinsky F (2021) IFN-γ mediates Paneth cell death via suppression of mTOR. eLife 10:e60478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bailey MT, Dowd SE, Parry NM, Galley JD, Schauer DB, Lyte M (2010) Stressor exposure disrupts commensal microbial populations in the intestines and leads to increased colonization by Citrobacter rodentium. Infect Immun 78(4):1509–1519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Besteiro S (2019) The role of host autophagy machinery in controlling Toxoplasma infection. Virulence 10(1):438–447

    Article  CAS  PubMed  Google Scholar 

  • Burger E, Araujo A, López-Yglesias A, Rajala MW, Geng L, Levine B, Hooper LV, Burstein E, Yarovinsky F (2018) Loss of Paneth cell autophagy causes acute susceptibility to Toxoplasma gondii-mediated inflammation. Cell Host Microbe 23(2):177–190. e4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chaichan P, Mercier A, Galal L, Mahittikorn A, Ariey F, Morand S, Boumediene F, Udonsom R, Hamidovic A, Murat JB (2017) Geographical distribution of Toxoplasma gondii genotypes in Asia: a link with neighboring continents. Infect Genet Evol 53:227–238

    Article  CAS  PubMed  Google Scholar 

  • Chang HR, Grau GE, Pechère JC (1990) Role of TNF and IL-1 in infections with Toxoplasma gondii. Immunology 69(1):33–37

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen ZW, Gao JM, Huo XX, Wang L, Yu L, Halm-Lai F, Xu YH, Song WJ, Hide G, Shen JL, Lun ZR (2011) Genotyping of Toxoplasma gondii isolates from cats in different geographic regions of China. Vet Parasitol 183:166–170

    Article  CAS  PubMed  Google Scholar 

  • Cohen SB, Denkers EY (2015) The gut mucosal immune response to Toxoplasma gondii. Parasite Immunol 37(3):108–117

    Article  CAS  PubMed  Google Scholar 

  • Cooper HS, Murthy SN, Shah RS, Sedergran DJ (1993) Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 69:238–249

    CAS  PubMed  Google Scholar 

  • Cui C, Wang F, Zheng Y, Wei H, Peng J (2023) From birth to death: the hardworking life of Paneth cell in the small intestine. Front immunol 14:1122258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dong H, Su R, Lu Y, Wang M, Liu J, Jian F, Yang Y (2018) Prevalence, risk factors, and genotypes of Toxoplasma gondii in food animals and humans (2000-2017) from China. Front Microbiol 9:2108

    Article  PubMed  PubMed Central  Google Scholar 

  • Dowd SE, Wolcott RD, Sun Y, McKeehan T, Smith E, Rhoads D (2008) Polymicrobial nature of chronic diabetic foot ulcer biofilm infections determined using bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP). PLoS One 3(10):e3326

    Article  PubMed  PubMed Central  Google Scholar 

  • Dubey JP (2010) Toxoplasmosis of animals and humans, second edn. CRC Press, Boca Raton, Florida, pp 1–313

    Google Scholar 

  • Dubey JP (2022) Toxoplasmosis of animals and humans, third edn. CRC Press, Boca Raton, Florida, pp 1–542

    Google Scholar 

  • Dubey JP, Desmonts G (1987) Serological responses of equids fed Toxoplasma gondii oocysts. Equine Vet J 19:337–339

    Article  CAS  PubMed  Google Scholar 

  • Dubey JP, Ferreira LR, Martins J, McLeod R (2012) Oral oocyst-induced mouse model of toxoplasmosis: effect of infection with Toxoplasma gondii strains of different genotypes, dose, and mouse strains (transgenic, out-bred, in-bred) on pathogenesis and mortality. Parasitology 139(1):1–13

    Article  CAS  PubMed  Google Scholar 

  • Dubey JP, Lunney JK, Shen SK, Kwok OCH, Ashford DA, Thulliez P (1996) Infectivity of low numbers of Toxoplasma gondii oocysts to pigs. J Parasitol 82:438–443

    Article  CAS  PubMed  Google Scholar 

  • Dubey JP, Zhu XQ, Sundar N, Zhang H, Kwok OCH, Su C (2007) Genetic and biologic characterization of Toxoplasma gondii isolates of cats from China. Vet Parasitol 145:352–356

    Article  CAS  PubMed  Google Scholar 

  • Eriguchi Y, Nakamura K, Yokoi Y, Sugimoto R, Takahashi S, Hashimoto D, Teshima T, Ayabe T, Selsted ME, Ouellette AJ (2018) Essential role of IFN-γ in T cell-associated intestinal inflammation. JCI Insight 3(18):pii: 121886

  • Gazzinelli RT, Wysocka M, Hayashi S, Denkers EY, Hieny S, Caspar P, Trinchieri G, Sher A (1994a) Parasite-induced IL-12 stimulates early IFN-gamma synthesis and resistance during acute infection with Toxoplasma gondii. J Immunol 153(6):2533–2543

    Article  CAS  PubMed  Google Scholar 

  • Gazzinelli RT, Wysocka M, Hieny S, Scharton-Kersten T, Cheever A, Kühn R, Müller W, Trinchieri G, Sher A (1996) In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha. J Immunol 157(2):798–805

    Article  CAS  PubMed  Google Scholar 

  • Gazzinelli RT, Hayashi S, Wysocka M, Carrera L, Kuhn R, Muller W, Roberge F, Trinchieri G, Sher A (1994b) Role of IL-12 in the initiation of cell mediated immunity by Toxoplasma gondii and its regulation by IL-10 and nitric oxide. J Eukaryot Microbiol 41(5):9S

    CAS  PubMed  Google Scholar 

  • Heimesaat MM, Escher U, Grunau A, Fiebiger U, Bereswill S (2018) Peroral low-dose Toxoplasma gondii infection of human microbiota-associated mice a subacute ileitis model to unravel pathogen–host interactions. Euro J microbiol immunol 8(2):53–61

    Article  CAS  Google Scholar 

  • Hunter CA, Subauste CS, Van Cleave VH, Remington JS (1994) Production of gamma interferon by natural killer cells from Toxoplasma gondii-infected SCID mice: regulation by interleukin-10, interleukin-12 and tumor necrosis factor alpha. Infect Immun 62(7):2818–2824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang N, Su RJ, Jian FC, Su CL, Zhang LX, Jiang YB, Yang YR (2020) Toxoplasma gondii in lambs of China: heart juice serology, isolation and genotyping. Inter J Food Microbiol 322:108563

    Article  CAS  Google Scholar 

  • Jiang Y, Xin S, Ma Y, Zhang H, Yang X, Yang Y (2023) Low prevalence of Toxoplasma gondii in sheep and isolation of a viable strain from edible mutton from central China. Pathogens 12(6):827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson LL (1992) A protective role for endogenous tumor necrosis factor in Toxoplasma gondii infection. Infect Immune 60(5):1979–1983

    Article  CAS  Google Scholar 

  • Kirkland D, Benson A, Mirpuri J, Pifer R, Hou B, DeFranco AL, Yarovinsky F (2012) B cell-intrinsic MyD88 signaling prevents the lethal dissemination of commensal bacteria during colonic damage. Immunity 36:228–238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klitzing EV, Ekmekciu I, Kühl AA, Bereswill S, Heimesaat MM (2017) Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota. PLoS One 12(4):e0176144

    Article  Google Scholar 

  • Lieberman LA, Hunter CA (2002) The role of cytokines and their signaling pathways in the regulation of immunity to Toxoplasma gondii. Int Rev Immunol 21(4-5):373–403

    Article  CAS  PubMed  Google Scholar 

  • 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(2):597–607

    Article  CAS  PubMed  Google Scholar 

  • Liesenfeld O, Kang H, Park D, Nguyen TA, Parkhe CV, Watanabe H, Abo T, Sher A, Remington JS, Suzuki Y (1999) 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(7):365–376

    Article  CAS  PubMed  Google Scholar 

  • Lu YY, Dong H, Feng YJ, Wang K, Jiang YB, Zhang LX, Yang YR (2018) Avirulence and lysozyme secretion in Paneth cells after infection of BALB/c mice with oocysts of Toxoplasma gondii strains TgCatCHn2 (ToxoDB#17) and TgCatCHn4 (ToxoDB#9). Vet Parasitol 252:1–8

    Article  CAS  PubMed  Google Scholar 

  • Martínez-Gómez F, García-González LF, Mondragón-Flores R, Bautista-Garfias CR (2009) Protection against Toxoplasma gondii brain cyst formation in mice immunized with Toxoplasma gondii cytoskeleton proteins and Lactobacillus casei as adjuvant. Vet Parasitol 160(3):311–315

    Article  PubMed  Google Scholar 

  • Mordue DG, Monroy F, La RM, Dinarello CA, Sibley LD (2001) Acute toxoplasmosis leads to lethal overproduction of Th1 cytokines. J Immunol 167(8):4574

    Article  CAS  PubMed  Google Scholar 

  • Parmley SF, Gross U, Sucharczuk A, Windeck T, Sgarlato GD, Remington JS (1994) Two alleles of the gene encoding surface antigen P22 in 25 strains of Toxoplasma gondii. J Parasitol 80:293–301

    Article  CAS  PubMed  Google Scholar 

  • Raetz M, Hwang SH, Wilhelm CL, Kirkland D, Benson A, Sturge CR, Mirpuri J, Vaishnava S, Hou B, Defranco AL, Gilpin CJ, Hooper LV, Yarovinsky F (2013) Parasite-induced TH1 cells and intestinal dysbiosis cooperate in IFN-γ-dependent elimination of Paneth cells. Nat Immunol 14(2):136–142

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro CM, Costa VM, Gomes MI, Golim MA, Modolo JR, Langoni H (2011) Effects of synbiotic-based Bifidobacterium animalis in female rats experimentally infected with Toxoplasma gondii. Com Immunol Microbiol Infec Dis 34(2):111–114

    Article  Google Scholar 

  • Ribeiro Cde M, Zorgi NE, Meireles LR, Garcia JL, de Andrade Junior HF (2016) CD19 lymphocyte proliferation induced by Bifidobacterium animalis subsp. lactis in C57BL/6 mice experimentally infected with Toxoplasma gondii. Revista Do Instituto De Medicina Tropical De São Paulo 58:26

    PubMed  Google Scholar 

  • Ruder B, Atreya R, Becker C (2019) Tumour necrosis factor alpha in intestinal homeostasis and gut related diseases. Int J Mol Sci 20(8):E1887

    Article  Google Scholar 

  • Scharton-Kersten TM, Wynn TA, Denkers EY, Bala S, Grunvald E, Hieny S, Gazzinelli RT, Sher A (1996) In the absence of endogenous IFN-gamma, mice develop unimpaired IL-12 responses to Toxoplasma gondii while failing to control acute infection. J Immunol 157(9):4045–4054

    Article  CAS  PubMed  Google Scholar 

  • Schreiner M, Liesenfeld O (2009) Small intestinal inflammation following oral infection with Toxoplasma gondii does not occur exclusively in C57BL/6 mice: review of 70 reports from the literature. Mem Inst Oswaldo Cruz 104(2):221–233

    Article  CAS  PubMed  Google Scholar 

  • Schweichel JU, Merker HJ (1973) The morphology of various types of cell death in prenatal tissues. Teratology 7(3):253–266

    Article  CAS  PubMed  Google Scholar 

  • Stappenbeck TS (2010) The role of autophagy in Paneth cell differentiation and secretion. Mucosal Immunol 3:8–10

    Article  CAS  PubMed  Google Scholar 

  • Su RJ, Dong H, Li TY, Jiang YB, Yuan ZG, Su CL, Zhang LX, Yang YR (2019) Toxoplasma gondii in four captive kangaroos (Macropus spp.) in China: isolation of a strain of a new genotype from an eastern grey kangaroo (Macropus giganteus). Int J Parasitol Parasites Wildl 8:234–239

    Article  PubMed  PubMed Central  Google Scholar 

  • Suzuki Y, Orellana MA, Schreiber RD, Remington JS (1988) Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science 240(4851):516–518

    Article  CAS  PubMed  Google Scholar 

  • Von KE, Ekmekciu I, Kühl AA, Bereswill S, Heimesaat MM (2017) Intestinal, extra-intestinal and systemic sequelae of T. gondii induced acute ileitis in mice harboring a human gut microbiota. PLoS One 12(4):e0176144

    Article  Google Scholar 

  • Walters W, Hyde ER, Berg-Lyons D, Ackermann G, Humphrey G, Parada A, Gilbert JA, Jansson JK, Caporaso JG, Fuhrman JA, Apprill A, Knight R (2015) Improved bacterial 16S rRNA Gene (V4 and V4-5) and fungal internal transcribed spacer marker gene primers for microbial community surveys. mSystems 1(1):e00009–e00015

    PubMed  PubMed Central  Google Scholar 

  • Weiss LM, Dubey JP (2009) Toxoplasmosis: a history of clinical observations. Int J Parasitol 39(8):895–901

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Dong H, Su R, Li T, Jiang N, Su C, Zhang L (2019) Evidence of red panda as an intermediate host of Toxoplasma gondii and Sarcocystis species. Int J Parasitol Parasites Wildl 8:188–191

    Article  PubMed  PubMed Central  Google Scholar 

  • Yuan J, Kroemer G (2010) Alternative cell death mechanisms in development and beyond. Genes Dev 24(23):2592–2602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang CF, Song YQ, Zhang TR, Wang JL (2016) Effects of intestinal microecological changes on the number of small intestine Paneth cells in mice. Heilongjiang Anim Sci Vet Med 9:224–226 in Chinese

    CAS  Google Scholar 

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Acknowledgements

We thank Jitender Prakash Dubey (US Department of Agriculture, Beltsville, MD, USA) for providing the VEG T. gondii strain and primary antibody against T. gondii. We are also grateful to Shimin Zheng (Northeast Agricultural University, China), Chunlei Su (University of Tennessee, Knoxville, USA), and Shuai Wang (Lanzhou Veterinary Research Institute, China) for their valuable suggestions. We thank Caili Zhang and Xianghua Liu of the TEM Center at the Henan University of Chinese Medicine for their assistance.

Funding

This study was financed by the Henan Province Modern Agricultural Industrial Technology System, China (mutton sheep: HARS-22-15-G1).

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  1. Veterinary Pathology, College of Veterinary Science, Henan Agricultural University, Zhengzhou, China

    Ruijing Su & Yurong Yang

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  1. Ruijing Su
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  2. Yurong Yang
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SRJ performed the laboratory tests and data analysis and wrote the manuscript. YRY designed the study protocol, analyzed the results, and wrote the manuscript. Both authors have read and approved the final version of the manuscript.

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Correspondence to Ruijing Su or Yurong Yang.

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The experimental protocol was established according to the ethical guidelines of the Institutional Animal Use Committee of Henan Agricultural University (China). The protocol was approved by the Beijing Association for Science and Technology (SYXK [Beijing] 2007–0023).

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Su, R., Yang, Y. Gut commensal bacteria exacerbate toxoplasmosis associated with TgSheepCHn5 (ToxoDB#2) and TgRedpandaCHn1 (ToxoDB#20) through Th1 immune response. Parasitol Res 122, 2795–2806 (2023). https://doi.org/10.1007/s00436-023-07962-9

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