The ROP16III-dependent early immune response determines the subacute CNS immune response and type III Toxoplasma gondii survival


Autoři: Shraddha Tuladhar aff001;  Joshua A. Kochanowsky aff001;  Apoorva Bhaskara aff002;  Yarah Ghotmi aff002;  Sambamurthy Chandrasekaran aff002;  Anita A. Koshy aff001
Působiště autorů: Department of Immunobiology, University of Arizona, Tucson, Arizona, United States of America aff001;  Bio5 Institute, University of Arizona, Tucson, Arizona, United States of America aff002;  Undergraduate Biology Research Program (UBRP), University of Arizona, Tucson, Arizona, United States of America aff003;  Department of Neurology, University of Arizona, Tucson, Arizona, United States of America aff004
Vyšlo v časopise: The ROP16III-dependent early immune response determines the subacute CNS immune response and type III Toxoplasma gondii survival. PLoS Pathog 15(10): e32767. doi:10.1371/journal.ppat.1007856
Kategorie: Research Article
doi: 10.1371/journal.ppat.1007856

Souhrn

Toxoplasma gondii is an intracellular parasite that persistently infects the CNS and that has genetically distinct strains which provoke different acute immune responses. How differences in the acute immune response affect the CNS immune response is unknown. To address this question, we used two persistent Toxoplasma strains (type II and type III) and examined the CNS immune response at 21 days post infection (dpi). Contrary to acute infection studies, type III-infected mice had higher numbers of total CNS T cells and macrophages/microglia but fewer alternatively activated macrophages (M2s) and regulatory T cells (Tregs) than type II-infected mice. By profiling splenocytes at 5, 10, and 21 dpi, we determined that at 5 dpi type III-infected mice had more M2s while type II-infected mice had more pro-inflammatory macrophages and that these responses flipped over time. To test how these early differences influence the CNS immune response, we engineered the type III strain to lack ROP16 (IIIΔrop16), the polymorphic effector protein that drives the early type III-associated M2 response. IIIΔrop16-infected mice showed a type II-like neuroinflammatory response with fewer infiltrating T cells and macrophages/microglia and more M2s and an unexpectedly low CNS parasite burden. At 5 dpi, IIIΔrop16-infected mice showed a mixed inflammatory response with more pro-inflammatory macrophages, M2s, T effector cells, and Tregs, and decreased rates of infection of peritoneal exudative cells (PECs). These data suggested that type III parasites need the early ROP16-associated M2 response to avoid clearance, possibly by the Immunity-Related GTPases (IRGs), which are IFN-γ- dependent proteins essential for murine defenses against Toxoplasma. To test this possibility, we infected IRG-deficient mice and found that IIIΔrop16 parasites now maintained parental levels of PECs infection. Collectively, these studies suggest that, for the type III strain, rop16III plays a key role in parasite persistence and influences the subacute CNS immune response.

Klíčová slova:

Central nervous system – Cloning – Cytotoxic T cells – Immune response – Macrophages – Parasitic diseases – T cells – Toxoplasma


Zdroje

1. Suzuki Y. Immunopathogenesis of Cerebral Toxoplasmosis. J Infect Dis. 2002 Dec 1;186:S234–40. doi: 10.1086/344276 12424703

2. Carruthers VB. Host cell invasion by the opportunistic pathogen Toxoplasma gondii. Acta Trop. 2002 Feb;81(2):111–22. doi: 10.1016/s0001-706x(01)00201-7 11801218

3. Hill D, Dubey JP. Toxoplasma gondii: transmission, diagnosis and prevention. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2002 Oct;8(10):634–40.

4. Wreghitt TG, Gray JJ, Pavel P, Balfour A, Fabbri A, Sharples LD, et al. Efficacy of pyrimethamine for the prevention of donor-acquired Toxoplasma gondii infection in heart and heart-lung transplant patients. Transpl Int Off J Eur Soc Organ Transplant. 1992 Sep;5(4):197–200.

5. Ruskin J, Remington JS. Toxoplasmosis in the compromised host. Ann Intern Med. 1976 Feb;84(2):193–9. doi: 10.7326/0003-4819-84-2-193 766683

6. Luft BJ, Remington JS. Toxoplasmic encephalitis in AIDS. Clin Infect Dis Off Publ Infect Dis Soc Am. 1992 Aug;15(2):211–22.

7. Desmonts G, Couvreur J. Congenital toxoplasmosis. A prospective study of 378 pregnancies. N Engl J Med. 1974 May 16;290(20):1110–6. doi: 10.1056/NEJM197405162902003 4821174

8. Grigg ME, Ganatra J, Boothroyd JC, Margolis TP. Unusual abundance of atypical strains associated with human ocular toxoplasmosis. J Infect Dis. 2001 Sep 1;184(5):633–9. doi: 10.1086/322800 11474426

9. Kamerkar S, Davis PH. Toxoplasma on the Brain: Understanding Host-Pathogen Interactions in Chronic CNS Infection. J Parasitol Res [Internet]. 2012 [cited 2013 Aug 10];2012. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321570/

10. Ferreira IMR, Vidal JE, de Mattos C de CB, de Matto LC, Qu D, Su C, et al. Toxoplasma gondii isolates: multilocus RFLP-PCR genotyping from human patients in Sao Paulo State, Brazil identified distinct genotypes. Exp Parasitol. 2011 Oct;129(2):190–5. doi: 10.1016/j.exppara.2011.06.002 21741380

11. Dubey JP, Lago EG, Gennari SM, Su C, Jones JL. Toxoplasmosis in humans and animals in Brazil: high prevalence, high burden of disease, and epidemiology. Parasitology. 2012 Sep;139(11):1375–424. doi: 10.1017/S0031182012000765 22776427

12. Furtado JM, Winthrop KL, Butler NJ, Smith JR. Ocular toxoplasmosis I: parasitology, epidemiology and public health. Clin Experiment Ophthalmol. 2013 Feb;41(1):82–94. doi: 10.1111/j.1442-9071.2012.02821.x 22594908

13. Remington JS, McLeod R, Wilson CB, Desmonts G. CHAPTER 31—Toxoplasmosis. In: Infectious Diseases of the Fetus and Newborn (Seventh Edition) [Internet]. Philadelphia: W.B. Saunders; 2011. p. 918–1041. https://www.sciencedirect.com/science/article/pii/B9781416064008000316

14. Boothroyd JC, Grigg ME. Population biology of Toxoplasma gondii and its relevance to human infection: do different strains cause different disease? Curr Opin Microbiol. 2002 Aug 1;5(4):438–42. 12160866

15. Sibley LD, Boothroyd JC. Virulent strains of Toxoplasma gondii comprise a single clonal lineage. Nature. 1992 Sep 3;359(6390):82–5. doi: 10.1038/359082a0 1355855

16. Howe DK, Sibley LD. Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease. J Infect Dis. 1995 Dec;172(6):1561–6. doi: 10.1093/infdis/172.6.1561 7594717

17. Su C, Khan A, Zhou P, Majumdar D, Ajzenberg D, Dardé M-L, et al. Globally diverse Toxoplasma gondii isolates comprise six major clades originating from a small number of distinct ancestral lineages. Proc Natl Acad Sci. 2012 Apr 10;109(15):5844–9. doi: 10.1073/pnas.1203190109 22431627

18. Saeij JPJ, Boyle JP, Coller S, Taylor S, Sibley LD, Brooke-Powell ET, et al. Polymorphic secreted kinases are key virulence factors in toxoplasmosis. Science. 2006 Dec 15;314(5806):1780–3. doi: 10.1126/science.1133690 17170306

19. Saeij JPJ, Coller S, Boyle JP, Jerome ME, White MW, Boothroyd JC. Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature. 2007 Jan 18;445(7125):324–7. doi: 10.1038/nature05395 17183270

20. Butcher BA, Fox BA, Rommereim LM, Kim SG, Maurer KJ, Yarovinsky F, et al. Toxoplasma gondii rhoptry kinase ROP16 activates STAT3 and STAT6 resulting in cytokine inhibition and arginase-1-dependent growth control. PLoS Pathog. 2011 Sep;7(9):e1002236. doi: 10.1371/journal.ppat.1002236 21931552

21. Rosowski EE, Lu D, Julien L, Rodda L, Gaiser RA, Jensen KDC, et al. Strain-specific activation of the NF-kappaB pathway by GRA15, a novel Toxoplasma gondii dense granule protein. J Exp Med. 2011 Jan 17;208(1):195–212. doi: 10.1084/jem.20100717 21199955

22. Jensen KDC, Wang Y, Wojno EDT, Shastri AJ, Hu K, Cornel L, et al. Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation. Cell Host Microbe. 2011 Jun 16;9(6):472–83. doi: 10.1016/j.chom.2011.04.015 21669396

23. Suzuki Y, Conley FK, Remington JS. Differences in virulence and development of encephalitis during chronic infection vary with the strain of Toxoplasma gondii. J Infect Dis. 1989 Apr;159(4):790–4. doi: 10.1093/infdis/159.4.790 2926171

24. Suzuki Y, Joh K. Effect of the strain of Toxoplasma gondii on the development of toxoplasmic encephalitis in mice treated with antibody to interferon-gamma. Parasitol Res. 1994;80(2):125–30. doi: 10.1007/bf00933779 8202451

25. Robben PM, Mordue DG, Truscott SM, Takeda K, Akira S, Sibley LD. Production of IL-12 by macrophages infected with Toxoplasma gondii depends on the parasite genotype. J Immunol Baltim Md 1950. 2004 Mar 15;172(6):3686–94.

26. Fentress SJ, Behnke MS, Dunay IR, Mashayekhi M, Rommereim LM, Fox BA, et al. Phosphorylation of immunity-related GTPases by a Toxoplasma gondii-secreted kinase promotes macrophage survival and virulence. Cell Host Microbe. 2010 Dec 16;8(6):484–95. doi: 10.1016/j.chom.2010.11.005 21147463

27. Niedelman W, Gold DA, Rosowski EE, Sprokholt JK, Lim D, Arenas AF, et al. The Rhoptry Proteins ROP18 and ROP5 Mediate Toxoplasma gondii Evasion of the Murine, But Not the Human, Interferon-Gamma Response. PLOS Pathog. 2012 Jun 28;8(6):e1002784. doi: 10.1371/journal.ppat.1002784 22761577

28. Henry SC, Daniell XG, Burroughs AR, Indaram M, Howell DN, Coers J, et al. Balance of Irgm protein activities determines IFN-γ-induced host defense. J Leukoc Biol. 2009;85(5):877–85. doi: 10.1189/jlb.1008599 19176402

29. Suzuki Y, Orellana MA, Schreiber RD, Remington JS. Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science. 1988 Apr 22;240(4851):516–8. doi: 10.1126/science.3128869 3128869

30. Suzuki Y, Conley FK, Remington JS. Treatment of toxoplasmic encephalitis in mice with recombinant gamma interferon. Infect Immun. 1990 Sep 1;58(9):3050–5. 2387632

31. Suzuki Y, Claflin J, Wang X, Lengi A, Kikuchi T. Microglia and macrophages as innate producers of interferon-gamma in the brain following infection with Toxoplasma gondii. Int J Parasitol. 2005 Jan;35(1):83–90. doi: 10.1016/j.ijpara.2004.10.020 15619519

32. Sa Q, Ochiai E, Tiwari A, Perkins S, Mullins J, Gehman M, et al. Cutting Edge: IFN-γ Produced by Brain-Resident Cells Is Crucial To Control Cerebral Infection with Toxoplasma gondii. J Immunol Baltim Md 1950. 2015 Aug 1;195(3):796–800.

33. Burg JL, Grover CM, Pouletty P, Boothroyd JC. Direct and sensitive detection of a pathogenic protozoan, Toxoplasma gondii, by polymerase chain reaction. J Clin Microbiol. 1989 Aug;27(8):1787–92. 2768467

34. Buchbinder S, Blatz R, Christian Rodloff A. Comparison of real-time PCR detection methods for B1 and P30 genes of Toxoplasma gondii. Diagn Microbiol Infect Dis. 2003 Apr;45(4):269–71. doi: 10.1016/s0732-8893(02)00549-7 12729998

35. Noor S, Habashy AS, Nance JP, Clark RT, Nemati K, Carson MJ, et al. CCR7-dependent immunity during acute Toxoplasma gondii infection. Infect Immun. 2010 May;78(5):2257–63. doi: 10.1128/IAI.01314-09 20194594

36. Cekanaviciute E, Dietrich HK, Axtell RC, Williams AM, Egusquiza R, Wai KM, et al. Astrocytic TGF-β signaling limits inflammation and reduces neuronal damage during central nervous system Toxoplasma infection. J Immunol Baltim Md 1950. 2014 Jul 1;193(1):139–49.

37. Knoll LJ, Boothroyd JC. Isolation of developmentally regulated genes from Toxoplasma gondii by a gene trap with the positive and negative selectable marker hypoxanthine-xanthine-guanine phosphoribosyltransferase. Mol Cell Biol. 1998 Feb;18(2):807–14. doi: 10.1128/mcb.18.2.807 9447977

38. O’Brien CA, Overall C, Konradt C, O’Hara Hall AC, Hayes NW, Wagage S, et al. CD11c-Expressing Cells Affect Regulatory T Cell Behavior in the Meninges during Central Nervous System Infection. J Immunol Baltim Md 1950. 2017 15;198(10):4054–61.

39. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014 Jul 17;41(1):14–20. doi: 10.1016/j.immuni.2014.06.008 25035950

40. Jin RM, Blair SJ, Warunek J, Heffner RR, Blader IJ, Wohlfert EA. Regulatory T Cells Promote Myositis and Muscle Damage in Toxoplasma gondii Infection. J Immunol Baltim Md 1950. 2017 1;198(1):352–62.

41. Benoit M, Desnues B, Mege J-L. Macrophage polarization in bacterial infections. J Immunol Baltim Md 1950. 2008 Sep 15;181(6):3733–9.

42. Nance JP, Vannella KM, Worth D, David C, Carter D, Noor S, et al. Chitinase dependent control of protozoan cyst burden in the brain. PLoS Pathog. 2012;8(11):e1002990. doi: 10.1371/journal.ppat.1002990 23209401

43. Pittman KJ, Cervantes PW, Knoll LJ. Z-DNA Binding Protein Mediates Host Control of Toxoplasma gondii Infection. Infect Immun. 2016;84(10):3063–70. doi: 10.1128/IAI.00511-16 27481249

44. Darwich L, Coma G, Peña R, Bellido R, Blanco EJJ, Este JA, et al. Secretion of interferon-γ by human macrophages demonstrated at the single-cell level after costimulation with interleukin (IL)-12 plus IL-18. Immunology. 2009;126(3):386–93. doi: 10.1111/j.1365-2567.2008.02905.x 18759749

45. Leopold Wager CM, Hole CR, Campuzano A, Castro-Lopez N, Cai H, Caballero Van Dyke MC, et al. IFN-γ immune priming of macrophages in vivo induces prolonged STAT1 binding and protection against Cryptococcus neoformans. PLoS Pathog. 2018;14(10):e1007358. doi: 10.1371/journal.ppat.1007358 30304063

46. Koshy AA, Dietrich HK, Christian DA, Melehani JH, Shastri AJ, Hunter CA, et al. Toxoplasma Co-opts Host Cells It Does Not Invade. PLoS Pathog. 2012 Jul 26;8(7):e1002825. doi: 10.1371/journal.ppat.1002825 22910631

47. Madisen L, Zwingman TA, Sunkin SM, Oh SW, Zariwala HA, Gu H, et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci. 2010 Jan;13(1):133–40. doi: 10.1038/nn.2467 20023653

48. Koshy AA, Fouts AE, Lodoen MB, Alkan O, Blau HM, Boothroyd JC. Toxoplasma secreting Cre recombinase for analysis of host-parasite interactions. Nat Methods. 2010 Apr;7(4):307–9. doi: 10.1038/nmeth.1438 20208532

49. Cabral CM, Tuladhar S, Dietrich HK, Nguyen E, MacDonald WR, Trivedi T, et al. Neurons are the Primary Target Cell for the Brain-Tropic Intracellular Parasite Toxoplasma gondii. PLoS Pathog. 2016 Feb;12(2):e1005447. doi: 10.1371/journal.ppat.1005447 26895155

50. Jensen KDC, Hu K, Whitmarsh RJ, Hassan MA, Julien L, Lu D, et al. Toxoplasma gondii Rhoptry 16 Kinase Promotes Host Resistance to Oral Infection and Intestinal Inflammation Only in the Context of the Dense Granule Protein GRA15. Infect Immun. 2013 Jun 1;81(6):2156–67. doi: 10.1128/IAI.01185-12 23545295

51. Xu S, Shinohara ML. Tissue-Resident Macrophages in Fungal Infections. Front Immunol. 2017;8:1798. doi: 10.3389/fimmu.2017.01798 29312319

52. Roberts CA, Dickinson AK, Taams LS. The Interplay Between Monocytes/Macrophages and CD4+ T Cell Subsets in Rheumatoid Arthritis. Front Immunol [Internet]. 2015 [cited 2019 Mar 3];6. https://www.frontiersin.org/articles/10.3389/fimmu.2015.00571/full

53. Mojica FJM, Díez-Villaseñor C, García-Martínez J, Soria E. Intervening Sequences of Regularly Spaced Prokaryotic Repeats Derive from Foreign Genetic Elements. J Mol Evol. 2005 Feb 1;60(2):174–82. doi: 10.1007/s00239-004-0046-3 15791728

54. Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nat Protoc Lond. 2013 Nov;8(11):2281–308.

55. Shen B, Brown KM, Lee TD, Sibley LD. Efficient gene disruption in diverse strains of Toxoplasma gondii using CRISPR/CAS9. mBio. 2014 May 13;5(3):e01114–01114. doi: 10.1128/mBio.01114-14 24825012

56. Sidik SM, Hackett CG, Tran F, Westwood NJ, Lourido S. Efficient Genome Engineering of Toxoplasma gondii Using CRISPR/Cas9. PLoS One San Franc. 2014 Jun;9(6):e100450.

57. Zhao YO, Khaminets A, Hunn JP, Howard JC. Disruption of the Toxoplasma gondii Parasitophorous Vacuole by IFNγ-Inducible Immunity-Related GTPases (IRG Proteins) Triggers Necrotic Cell Death. PLoS Pathog. 2009 Feb 6;5(2):e1000288. doi: 10.1371/journal.ppat.1000288 19197351

58. Haldar AK, Saka HA, Piro AS, Dunn JD, Henry SC, Taylor GA, et al. IRG and GBP Host Resistance Factors Target Aberrant, “Non-self” Vacuoles Characterized by the Missing of “Self” IRGM Proteins. PLOS Pathog. 2013 Jun 13;9(6):e1003414. doi: 10.1371/journal.ppat.1003414 23785284

59. Coers J, Gondek DC, Olive AJ, Rohlfing A, Taylor GA, Starnbach MN. Compensatory T Cell Responses in IRG-Deficient Mice Prevent Sustained Chlamydia trachomatis Infections. PLOS Pathog. 2011 Jun 23;7(6):e1001346. doi: 10.1371/journal.ppat.1001346 21731484

60. Coers J, Bernstein-Hanley I, Grotsky D, Parvanova I, Howard JC, Taylor GA, et al. Chlamydia muridarum Evades Growth Restriction by the IFN-γ-Inducible Host Resistance Factor Irgb10. J Immunol. 2008 May 1;180(9):6237–45. doi: 10.4049/jimmunol.180.9.6237 18424746

61. Feng CG, Zheng L, Jankovic D, Báfica A, Cannons JL, Watford WT, et al. The immunity-related GTPase Irgm1 promotes the expansion of activated CD4+ T cell populations by preventing interferon-γ-induced cell death. Nat Immunol. 2008 Nov;9(11):1279–87. doi: 10.1038/ni.1653 18806793

62. Taylor S, Barragan A, Su C, Fux B, Fentress SJ, Tang K, et al. A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii. Science. 2006 Dec 15;314(5806):1776–80. doi: 10.1126/science.1133643 17170305

63. Ong Y-C, Reese ML, Boothroyd JC. Toxoplasma rhoptry protein 16 (ROP16) subverts host function by direct tyrosine phosphorylation of STAT6. J Biol Chem. 2010 Sep 10;285(37):28731–40. doi: 10.1074/jbc.M110.112359 20624917

64. Hickey WF, Kimura H. Graft-vs.-host disease elicits expression of class I and class II histocompatibility antigens and the presence of scattered T lymphocytes in rat central nervous system. Proc Natl Acad Sci. 1987 Apr 1;84(7):2082–6. doi: 10.1073/pnas.84.7.2082 3550805

65. Cabral CM, McGovern KE, MacDonald WR, Franco J, Koshy AA. Dissecting Amyloid Beta Deposition Using Distinct Strains of the Neurotropic Parasite Toxoplasma gondii as a Novel Tool. ASN Neuro. 2017 Aug;9(4):1759091417724915. doi: 10.1177/1759091417724915 28817954

66. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012 Jun 28;9(7):676–82. doi: 10.1038/nmeth.2019 22743772

67. Chan ED, Riches DW. IFN-gamma + LPS induction of iNOS is modulated by ERK, JNK/SAPK, and p38(mapk) in a mouse macrophage cell line. Am J Physiol Cell Physiol. 2001 Mar;280(3):C441–450. doi: 10.1152/ajpcell.2001.280.3.C441 11171562

68. Knoll LJ, Boothroyd JC. Isolation of Developmentally Regulated Genes from Toxoplasma gondii by a Gene Trap with the Positive and Negative Selectable Marker Hypoxanthine-Xanthine-Guanine Phosphoribosyltransferase. Mol Cell Biol. 1998 Feb;18(2):807–14. doi: 10.1128/mcb.18.2.807 9447977

69. Fux B, Nawas J, Khan A, Gill DB, Su C, Sibley LD. Toxoplasma gondii Strains Defective in Oral Transmission Are Also Defective in Developmental Stage Differentiation. Infect Immun. 2007 May;75(5):2580–90. doi: 10.1128/IAI.00085-07 17339346

70. Schaeffer M, Han S-J, Chtanova T, van Dooren GG, Herzmark P, Chen Y, et al. Dynamic Imaging of T Cell-Parasite Interactions in the Brains of Mice Chronically Infected with Toxoplasma gondii. J Immunol. 2009 May 15;182(10):6379–93. doi: 10.4049/jimmunol.0804307 19414791

71. Landrith TA, Sureshchandra S, Rivera A, Jang JC, Rais M, Nair MG, et al. CD103+ CD8 T Cells in the Toxoplasma-Infected Brain Exhibit a Tissue-Resident Memory Transcriptional Profile. Front Immunol. 2017;8:335. doi: 10.3389/fimmu.2017.00335 28424687

72. Barrigan LM, Tuladhar S, Brunton JC, Woolard MD, Chen C, Saini D, et al. Infection with Francisella tularensis LVS clpB leads to an altered yet protective immune response. Infect Immun. 2013 Jun;81(6):2028–42. doi: 10.1128/IAI.00207-13 23529616

73. Shen B, Brown K, Long S, Sibley LD. Development of CRISPR/Cas9 for Efficient Genome Editing in Toxoplasma gondii. Methods Mol Biol Clifton NJ. 2017;1498:79–103.

74. Pernas L, Boothroyd JC. Association of host mitochondria with the parasitophorous vacuole during Toxoplasma infection is not dependent on rhoptry proteins ROP2/8. Int J Parasitol. 2010 Oct;40(12):1367–71. doi: 10.1016/j.ijpara.2010.07.002 20637758

75. Donald RG, Roos DS. Insertional mutagenesis and marker rescue in a protozoan parasite: cloning of the uracil phosphoribosyltransferase locus from Toxoplasma gondii. Proc Natl Acad Sci. 1995 Jun 6;92(12):5749–53. doi: 10.1073/pnas.92.12.5749 7777580

76. Kafsack BFC, Carruthers VB, Pineda FJ. Kinetic modeling of Toxoplasma gondii invasion. J Theor Biol. 2007 Dec 21;249(4):817–25. doi: 10.1016/j.jtbi.2007.09.008 17942124

77. Ander SE, Rudzki EN, Arora N, Sadovsky Y, Coyne CB, Boyle JP. Human Placental Syncytiotrophoblasts Restrict Toxoplasma gondii Attachment and Replication and Respond to Infection by Producing Immunomodulatory Chemokines. Boothroyd JC, editor. mBio [Internet]. 2018 Jan 9 [cited 2019 Sep 13];9(1). https://mbio.asm.org/lookup/doi/10.1128/mBio.01678-17

78. Burg JL, Perelman D, Kasper LH, Ware PL, Boothroyd JC. Molecular analysis of the gene encoding the major surface antigen of Toxoplasma gondii. J Immunol Baltim Md 1950. 1988 Nov 15;141(10):3584–91.

Štítky
Hygiena a epidemiologie Infekční lékařství Laboratoř

Článek vyšel v časopise

PLOS Pathogens


2019 Číslo 10

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Farmaceutická péče o pacienta s inhalační terapií
nový kurz
Autoři: Mgr. Ondřej Šimandl

Revmatoidní artritida: včas a k cíli
Autoři: MUDr. Heřman Mann

Jistoty a nástrahy antikoagulační léčby aneb kardiolog - neurolog - farmakolog - nefrolog - právník diskutují
Autoři: doc. MUDr. Štěpán Havránek, Ph.D., prof. MUDr. Roman Herzig, Ph.D., doc. MUDr. Karel Urbánek, Ph.D., prim. MUDr. Jan Vachek, MUDr. et Mgr. Jolana Těšínová, Ph.D.

Léčba akutní pooperační bolesti
Autoři: doc. MUDr. Jiří Málek, CSc.

Nové antipsychotikum kariprazin v léčbě schizofrenie
Autoři: prof. MUDr. Cyril Höschl, DrSc., FRCPsych.

Všechny kurzy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se