Serotyping, host genes and cytokines response in human ocular toxoplasmosis

Mantilla-Muriel, Luz Eliana; Hernández-de-los-Ríos, Alejandro; Rincón, Mónica; de-la-Torre, Alejandra; Murillo-León, Mateo; Cardona, Néstor; Mercier, Corinne; Sepúlveda-Arias, Juan Carlos; Gómez-Marín, Jorge Enrique

doi:10.1016/j.micpath.2020.104465

Cited by 19 publications

(16 citation statements)

References 28 publications

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“…In USA, serotype II was also associated with congenital toxoplasmosis ( 43 ). In contrast, serotypes I/III are more prevalent in South America, where non-archetypal genotypes prevail ( 26 , 28 , 30 , 37 , 44 , 45 ). Few serotyping studies have been conducted in sera of African origin.…”

Section: Serological Signature Geographic Origin and Disease Outcomementioning

confidence: 94%

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Serotyping, a challenging approach for Toxoplasma gondii typing

2023

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Genotype analysis has revealed a high genetic diversity in strains of Toxoplasma gondii, isolated from a wide range of intermediate hosts and different geographic origins. Diversity is notably striking for parasites from wild hosts in South America, generally referred as non-archetypal genotypes. Those genotypes are implicated in the etiology of severe clinical disease, multivisceral toxoplasmosis, associated with high rate of mortality in immunocompetent individuals. Can we accept specific antibodies produced during T. gondii infection as biomarkers to identify infecting genotypes? Scientific evidence supports a positive response to this question; however, the genetic diversity of T. gondii genotypes organized into 16 haplogroups and collectively defined in 6 major clades, provides a reminder of the complexity and difficulty for the purpose. This review discusses serological approaches to genotyping T. gondii.

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Section: Serological Signature Geographic Origin and Disease Outcomementioning

confidence: 94%

“…However, as in South America, serotype I/III was also more prevalent than serotype II ( 28 ). Serotype I was associated with retinal lesions in patients from Colombia ( 45 ), and was the most frequent among congenital infections in Mexico ( 37 ).…”

Section: Serological Signature Geographic Origin and Disease Outcomementioning

confidence: 99%

Serotyping, a challenging approach for Toxoplasma gondii typing

2023

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“…T. gondii is an activator of the NLRP1 and NLRP3 inflammasomes in vivo [36,37] and an association of polymorphisms in human Nlrp1 and P2RX7 with susceptibility to congenital and ocular toxoplasmosis was reported [38][39][40][41][42][43]. Modulation of inflammasomes is critical to promote pathogen virulence and like many other vertebrate adapted pathogens, T. gondii inhibits IL-1β production.…”

Section: Introductionmentioning

confidence: 99%

Dual role of Toxoplasma gondii ROP5 and ROP18 for NLRP3 inhibition

Murillo-Leon,

Bastidas Quintero,

Singh

et al. 2023

Preprint

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Inflammasome activation leads release of IL-1b, a proinflammatory cytokine that drives antimicrobial immune responses. Toxoplasma gondii has been shown to activate the NLRP3 inflammasome but the trigger has not yet been identified. Here we provide evidence that vacuolar disruption is a prerequisite for NLRP3 activation. T. gondii type I ROP5 and ROP18 protect the parasitophorous vacuolar membrane (PVM) and thereby inhibit inflammasome activation and IL-1b release. Besides protection of the PVM, we demonstrate an additional function of ROP5 and ROP18 for NLRP3 inhibition. We demonstrate the molecular mechanism of this inhibition includes direct interaction with GBP5. In conclusion, T. gondii ROP5 and ROP18 inhibit IL-1β production by protection of the intracellular replicative niche of the parasite and by actively subverting NLRP3 activation. Our findings provide further insight into the intricate mechanisms governing inflammasome activation and inhibition, enhancing our understanding of the complex dynamics during T. gondii infection.

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“…Additionally, the predominant clonal lineage in East Asia, particularly in China, has been reported as the Chinese 1 genotype (ToxoDB#9) [ 4 , 5 ]. Both the severity of an episode and the chances of recurrence are related to the serotype of the parasite and the conditioned cytokine response of the host [ 6 ]. Patients infected by atypical strains have a specific intraocular cytokine pattern and retinochoroiditis toxoplasmosis susceptibility is linked to polymorphisms in cytokine genes [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

LFA-1/ ICAM-1 promotes NK cell cytotoxicity associated with the pathogenesis of ocular toxoplasmosis in murine model

Gao

Wang

et al. 2022

PLoS Negl Trop Dis

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Ocular toxoplasmosis (OT) is one of the most common causes of posterior uveitis. However, the pathogenic mechanisms of OT have not been well elucidated. Here, we used C57BL/6 (B6) mice to establish OT by peroral infection with 20 cysts of the TgCtWh6 strain, and severe ocular damage was observed by histopathological analysis in the eyes of infected mice. RNA-sequencing results showed that infection with T. gondii increased the expression of the NK-mediated cytotoxicity gene pathway at Day 30 after ocular T. gondii infection. Both NK-cell and CD49a+ NK-cell subsets are increased in ocular tissues, and the expression levels of LFA-1 in NK cells and ICAM-1 in the OT murine model were upregulated upon infection. Furthermore, inhibition of the interaction between LFA-1 and ICAM-1 with lifitegrast, a novel small molecule integrin antagonist, inhibited the protein expression of LFA-1 and ICAM-1 in murine OT and NK cells, improved the pathology of murine OT and influenced the secretion of cytokines in the OT murine model. In conclusion, the interaction between LFA-1 and ICAM-1 plays a role in the early regulation of the CD49a+ NK-cell proportion in an OT murine model. LFA-1/ ICAM-1 may be a key molecule in the pathogenesis of OT, and may provide new insights for potential immunotherapy.

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Serotyping, host genes and cytokines response in human ocular toxoplasmosis

Cited by 19 publications

References 28 publications

Serotyping, a challenging approach for Toxoplasma gondii typing

Serotyping, a challenging approach for Toxoplasma gondii typing

Dual role of Toxoplasma gondii ROP5 and ROP18 for NLRP3 inhibition

LFA-1/ ICAM-1 promotes NK cell cytotoxicity associated with the pathogenesis of ocular toxoplasmosis in murine model

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