Factors determining resistance and susceptibility to infection with Toxoplasma gondii

The ROP18 kinase has been identified as a key virulence determinant conferring a high mortality phenotype characteristic of type I Toxoplasma gondii strains. This major effector molecule is secreted by the rhoptries into the host cells during invasion; however, the molecular mechanisms by which this kinase exerts its pathogenic action remain poorly understood. In this study, we show that ROP18 targets the host endoplasmic reticulum–bound transcription factor ATF6β. Disruption of the ROP18 gene severely impairs acute toxoplasmosis by the type I RH strain. Because another virulence factor ROP16 kinase modulates immune responses through its N-terminal portion, we focus on the role of the N terminus of ROP18 in the subversion of host cellular functions. The N-terminal extension of ROP18 contributes to ATF6β-dependent pathogenicity by interacting with ATF6β and destabilizing it. The kinase activity of ROP18 is essential for proteasome-dependent degradation of ATF6β and for parasite virulence. Consistent with a key role for ATF6β in resistance against this intracellular pathogen, ATF6β-deficient mice exhibit a high susceptibility to infection by ROP18-deficient parasites. The results reveal that interference with ATF6β-dependent immune responses is a novel pathogenic mechanism induced by ROP18.

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Toxoplasma gondii: Impaired maturation and pro-inflammatory response of dendritic cells in MIF-deficient mice favors susceptibility to infection

Experimental Parasitology ◽

10.1016/j.exppara.2010.03.009 ◽

2010 ◽

Vol 126 (3) ◽

pp. 348-358 ◽

Cited By ~ 20

Author(s):

Cesar A. Terrazas ◽

Imelda Juarez ◽

Luis I. Terrazas ◽

Rafael Saavedra ◽

Elsa A. Calleja ◽

...

Keyword(s):

Dendritic Cells ◽

Toxoplasma Gondii ◽

Inflammatory Response ◽

Susceptibility To Infection ◽

Deficient Mice

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Impaired Innate Immunity in Mice Deficient in Interleukin-1 Receptor-Associated Kinase 4 Leads to Defective Type 1 T Cell Responses, B Cell Expansion, and Enhanced Susceptibility to Infection with Toxoplasma gondii

Infection and Immunity ◽

10.1128/iai.00328-12 ◽

2012 ◽

Vol 80 (12) ◽

pp. 4298-4308 ◽

Cited By ~ 14

Author(s):

Samantha R. Béla ◽

Míriam S. Dutra ◽

Ernest Mui ◽

Alexandre Montpetit ◽

Fernanda S. Oliveira ◽

...

Keyword(s):

Toxoplasma Gondii ◽

B Cell ◽

Cell Activation ◽

Interleukin 1 ◽

Congenital Toxoplasmosis ◽

Adaptor Protein ◽

Nucleotide Polymorphisms ◽

Content Type ◽

Susceptibility To Infection ◽

Resistance To Infection

ABSTRACTInterleukin-1 receptor (IL1R)-associated kinase 4 (IRAK4) is a member of the IRAK family and has an important role in inducing the production of inflammatory mediators. This kinase is downstream of MyD88, an adaptor protein essential for Toll-like receptor (TLR) function. We investigated the role of this kinase in IRAK4-deficient mice orally infected with the cystogenic ME49 strain ofToxoplasma gondii. IRAK4−/−mice displayed higher morbidity, tissue parasitism, and accelerated mortality than the control mice. The lymphoid follicles and germinal centers from infected IRAK4−/−mice were significantly smaller. We consistently found that IRAK4−/−mice showed a defect in splenic B cell activation and expansion as well as diminished production of gamma interferon (IFN-γ) by T lymphocytes. The myeloid compartment was also affected. Both the frequency and ability of dendritic cells (DCs) and monocytes/macrophages to produce IL-12 were significantly decreased, and resistance to infection withToxoplasmawas rescued by treating IRAK4−/−mice with recombinant IL-12 (rIL-12). Additionally, we report the association of IRAK4 haplotype-tagging single nucleotide polymorphisms (tag-SNPs) with congenital toxoplasmosis in infected individuals (rs1461567 and rs4251513,P< 0.023 andP< 0.045, respectively). Thus, signaling via IRAK4 is essential for the activation of innate immune cells, development of parasite-specific acquired immunity, and host resistance to infection withT. gondii.

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RESPONSES OF PLANTS TO INFECTION BY BOTRYTIS CINEREA AND NOVEL MEANS INVOLVED IN REDUCING THEIR SUSCEPTIBILITY TO INFECTION

Biological Reviews of the Cambridge Philosophical Society ◽

10.1017/s0006323197005057 ◽

1997 ◽

Vol 72 (3) ◽

pp. 381-422 ◽

Cited By ~ 64

Author(s):

Y. ELAD

Keyword(s):

Botrytis Cinerea ◽

Susceptibility To Infection

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Vorkommen und Genotypen von Toxoplasma gondii in der Muskulatur von Schaf, Rind und Schwein sowie im Katzenkot in der Schweiz

Schweizer Archiv für Tierheilkunde ◽

10.1024/0036-7281/a000341 ◽

2012 ◽

Vol 154 (6) ◽

pp. 251-255 ◽

Cited By ~ 9

Author(s):

F. C. Frey ◽

E. A. Berger-Schoch ◽

C. D. Herrmann ◽

G. Schares ◽

N. Müller ◽

...

Keyword(s):

Toxoplasma Gondii

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Altered visual attention behavior of Toxoplasma gondii-infected individuals.

Psychology & Neuroscience ◽

10.1037/pne0000179 ◽

2019 ◽

Vol 12 (4) ◽

pp. 485-494

Author(s):

Joaquim C. Rossini ◽

Carolina S. Lopes ◽

Fernanda P. Dirscherl ◽

Deise A. O. Silva ◽

José R. Mineo

Keyword(s):

Toxoplasma Gondii ◽

Visual Attention

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Konnatale Toxoplasmose

Kinder- und Jugendmedizin ◽

10.1055/s-0038-1629380 ◽

2014 ◽

Vol 14 (02) ◽

pp. 101-106

Author(s):

C. Feiterna-Sperling

Keyword(s):

Toxoplasma Gondii

ZusammenfassungBei einer primären Toxoplasmose in der Schwangerschaft besteht für den Fetus das Risiko einer konnatalen Infektion durch diaplazentare Transmission von Toxoplasma gondii. Das Risiko einer fetalen Infektion nimmt dabei mit der Schwangerschaftsdauer zu, während die Schwere der Symptomatik mit zunehmendem Gestationsalter abnimmt. Bei den meisten infizierten Neugeborenen finden sich klinisch inapparente Infektionen, aber auch postnatal unauffällige Kinder sind einem Risiko von späteren Folgeschäden ausgesetzt. Neben neurologischen Entwicklungsstörungen ist vor allem das Risiko einer Retinochoroiditis von Bedeutung, die sich auch erst im späteren Leben manifestieren kann. Eine frühzeitige Erkennung einer Primärinfektion in der Schwangerschaft ist Voraussetzung, um durch eine frühzeitige anti-parasitäre Therapie, das Risiko einer fetalen Schädigung zu reduzieren. Durch eine post-natale Therapie kann vermutlich zusätzlich das Risiko der Langzeitkomplikationen gesenkt werden. Neugeborene mit Verdacht auf eine konnatale Toxoplasmose müssen sorgfältig hinsichtlich einer konnatalen Infektion untersucht werden und Säuglinge mit einer gesicherten Infektion benötigen langfristige Nachuntersuchungen hinsichtlich möglicher Spätschäden, insbesondere der Manifestation einer Retinochoroiditis.

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Specific IgM to Toxoplasma gondii, Rubella and Cytomegalovirus Infection in First Trimester Miscarriage with Seasonal Variation

Al-Anbar Medical Journal ◽

10.33091/amj.0501412017 ◽

2017 ◽

Vol 14 (1) ◽

Keyword(s):

Seasonal Variation ◽

Toxoplasma Gondii ◽

Cytomegalovirus Infection ◽

First Trimester

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Gene Polymorphisms and Their Association to Coronavirus Family Infections: Susceptibility in Different Populations

Medical & Clinical Research ◽

10.33140/mcr.05.012 ◽

2020 ◽

Vol 5 ◽

Keyword(s):

Genetic Variants ◽

Viral Infections ◽

Human Leukocyte ◽

Asian Population ◽

African Region ◽

Mediterranean Populations ◽

Susceptibility To Infection ◽

Asian Populations ◽

Spread Pattern ◽

Different Populations

Human leukocyte antigen (HLA) loci are highly polymorphic and determine differential features of the immune response in subjects from different regions. HLA genes have been proposed to determine genetic susceptibility to several diseases, particularly to viral infections. Moreover, it has been suggested that each ethnic group could have a different specificity of T-lymphocyte reactivity to the same viral infections. In this review, we analyzed the distribution of HLA types in countries of the Asian, European and North African region. Also, we studied the relation between these HLA polymorphisms and susceptibility to infection by the coronavirus. Our findings indicated that homozygosity would increase susceptibility to viral infections and, in some cases, to coronavirus infection. HLA types showing higher susceptibility were reported in Asian population, including China, Singapore, and Taiwan. In contrast, lower susceptibility HLA variants were detected among African populations, some Asian populations, and Mediterranean populations. The presented evidence along with the spread pattern of COVID-19 infection suggests that HLA genetic variants might be related to its infection susceptibility and severity. The investigation of HLA genetic variants distribution would be a useful tool to predict different populations’ susceptibility to viral infections.

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