Mechanisms of Human Innate Immune Evasion by Toxoplasma gondii

Lima, Tatiane S.; Lodoen, Melissa B.

doi:10.3389/fcimb.2019.00103

Cited by 131 publications

(112 citation statements)

References 81 publications

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“…Additionally, macrophages are the first line of defense during acute toxoplasmosis (Kato, 2018;Lima and Lodoen, 2019); therefore, increasing the drug uptake by macrophages is the most important challenge during treatment of acute toxoplasmosis. Mannose receptor, known as CD206, is mostly expressed by macrophages and dendritic cells.…”

Section: Discussionmentioning

confidence: 99%

In vitro Evaluation of Mannosylated Paromomycin-Loaded Solid Lipid Nanoparticles on Acute Toxoplasmosis

Khosravi

Rahimi

Doroud

et al. 2020

Front. Cell. Infect. Microbiol.

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Toxoplasma gondii is a zoonotic intracellular protozoan with worldwide distribution. Acute and severe toxoplasmosis are commonly reported in patients who suffer from acquired/congenital immune deficiency. This study aimed to synthesize mannosylated paromomycin-loaded solid lipid nanoparticles (PM-SLN-M) and to evaluate them on acute toxoplasmosis. SLN was synthesized and then loaded by 7 mg/mL paromomycin sodium. Mannose coating was performed, and after washing, the size, zeta potential, and loading percentage were calculated. To evaluate the cell toxicity, an MTT assay was performed on Vero cells by different concentrations (log 10 −1) of SLN, PM-SLN-M, and PM-SLN. In addition, the anti-Toxoplasma effects were also evaluated using trypan-blue staining and scanning electron microscopy (SEM). An MTT assay was also employed to evaluate the effects of PM and PM-SLN-M on intracellular Toxoplasma. A 6-month stability test of PM-SLN and PM-SLN-M represented that the characteristics all remained constant. The cell viability assay demonstrated that PM-SLN-M had lower cell toxicity (<20%) compared to PM-SLN (<30%) and PM (<40%). Statistical analysis showed that PM-SLN-M significantly killed ∼97.555 ± 0.629 (95% CI: 91.901 to 103.209; P < 0.05) of T. gondii tachyzoites. More than 50% of Toxoplasma-infected Vero cells remained viable in concentrations more than 0.07 µg/mL and 7 µg/mL of PM and PM-SLN-M, respectively. SEM analysis showed that T. gondii tachyzoites were changed in both size and morphology facing with PM-SLN-M. Our findings indicated that synthesized PM-SLN-M had anti-Toxoplasma activity without significant host cell toxicity at the highest concentration. Our study demonstrated that PM was able to kill intracellular Toxoplasma in lower concentration in comparison to PM-SLN-M, although PM-SLN-M showed lower cytotoxic effects on Vero cells.

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Section: Discussionmentioning

confidence: 99%

In vitro Evaluation of Mannosylated Paromomycin-Loaded Solid Lipid Nanoparticles on Acute Toxoplasmosis

Khosravi

Rahimi

Doroud

et al. 2020

Front. Cell. Infect. Microbiol.

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“…Toxoplasma gondii, the causative agent of the neglected parasitic disease toxoplasmosis, is an obligate intracellular protozoan capable of infecting most types of mammalian cells. Toxoplasmosis affects 25-30% of humans worldwide and is usually asymptomatic in immunocompetent individuals, but can become a life threatening condition in immunocompromised patients as well as in developing fetuses (Delgado Betancourt et al, 2019;Lima and Lodoen, 2019). Toxoplasmosis can be transmitted via consumption of contaminated food, zoonotically or congenitally (Delgado Betancourt et al, 2019).…”

Section: Toxoplasmamentioning

confidence: 99%

“…Once an individual becomes infected, the parasite can disseminate through the bloodstream and establish a chronic infection in different organs. The three canonical types of toxoplasmosis are cerebral, lymphatic and ocular (Lima and Lodoen, 2019). After the entry of infected tachyzoids into the host intestine, a rapid recruitment of neutrophils occurs, followed by the action of other immune cells such as macrophages and dendritic cells.…”

Section: Toxoplasmamentioning

confidence: 99%

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The IL-33/ST2 Axis in Immune Responses Against Parasitic Disease: Potential Therapeutic Applications

Ryan

Anderson

Volpedo

et al. 2020

Front. Cell. Infect. Microbiol.

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Parasitic infections pose a wide and varying threat globally, impacting over 25% of the global population with many more at risk of infection. These infections are comprised of, but not limited to, toxoplasmosis, malaria, leishmaniasis and any one of a wide variety of helminthic infections. While a great deal is understood about the adaptive immune response to each of these parasites, there remains a need to further elucidate the early innate immune response. Interleukin-33 is being revealed as one of the earliest players in the cytokine milieu responding to parasitic invasion, and as such has been given the name "alarmin." A nuclear cytokine, interleukin-33 is housed primarily within epithelial and fibroblastic tissues and is released upon cellular damage or death. Evidence has shown that interleukin-33 seems to play a crucial role in priming the immune system toward a strong T helper type 2 immune response, necessary in the clearance of some parasites, while disease exacerbating in the context of others. With the possibility of being a double-edged sword, a great deal remains to be seen in how interleukin-33 and its receptor ST2 are involved in the immune response different parasites elicit, and how those parasites may manipulate or evade this host mechanism. In this review article we compile the current cutting-edge research into the interleukin-33 response to toxoplasmosis, malaria, leishmania, and helminthic infection. Furthermore, we provide insight into directions interleukin-33 research may take in the future, potential immunotherapeutic applications of interleukin-33 modulation and how a better clarity of early innate immune system responses involving interleukin-33/ST2 signaling may be applied in development of much needed treatment options against parasitic invaders.

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“…Toxoplasmosis is still a neglected tropical parasitic infection even 110 years after its discovery [4]. It is a cosmopolitan parasitic infection caused by an intracellular protozoan Toxoplasma gondii (T gondii) that is widespread throughout the world; with one third of the world population having been in contact with the parasite [3,5].…”

Section: Introductionmentioning

confidence: 99%

High viremia and Poor Immunity are Potential Surrogates of Anti-toxoplasmic Immunoglobulin G Quantification among HIV-Infected Individuals: A Cross-sectional Study in Yaoundé, Cameroon

Ka’e¹,

Sosso²,

Fokam³

et al. 2020

Preprint

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Background: Toxoplasmosis remains a neglected common opportunistic infection in immunocompromised individuals, who are mainly people living with HIV (PLWHIV) in whom reactivation of toxoplasmosis may occur with advanced HIV conditions in resource-limited settings (RLS). Our objective was to evaluate the correlation between the anti-toxoplasmic IgG (Tg-IgG) concentration and the immuno-virological status of PLWHIV.Methods : A prospective and cross-sectional study was conducted among PLWHIV aged>18 years from February to November 2018 at the Chantal BIYA international Reference Centre. Blood samples were collected from eligible consenting PLWHIV; Tg-IgG level was assessed by quantitative ELISA, CD4-T lymphocytes counts were measured by flow cytometry and HIV-1 plasma viral load (PVL) measurement by real-time-PCR. Data were analysed using Excel and Graph Pad softwares; with p<0.05 considered statistically significant.Results : A total of 100 PLWHIV were enrolled: 56% seropositive for IgG anti- Toxoplasma gondii, 33% seronegative and 11% indeterminate results. According to viremia, 100% (19/19) of those with PVL>1000 copies/mL were seropositive to Tg-IgG versus 52.85% (37/70) of those with PVL<1000 copies/mL (median [IQR] IgG concentration 152.78 [139.24-444.43] versus 34.44 [13.04-36.47] IU/mL, respectively); p<0.0001. According to CD4, 100% (11/11) of those with T-CD4<200 cells/µL were seropositive to Tg-IgG versus 57.69% (45/78) of those with T-CD4>200 cells/µL (median IgG [IQR] 432.92 [145.06-450.47] versus 35.01 [15.01-38.01] IU/mL, respectively); p<0.0001. Interestingly, there were moderate-positive and strong-negative correlations respectively with HIV-1 PVL (r = 0.54; p<0.0001) and T-CD4 (r = -0.70; p<0.0001) as compared to Tg-IgG concentration. After adjusting for age, gender, immune status and PVL in logistic regression, only poor immune status (T-CD4<200 cells/µL) was independently associated to Tg-IgG seropositivity (p=0.0004).Conclusion : In a typical RLS like Cameroon, about half of PLWHIV might be seropositive to Tg-IgG. Of relevance, decreasing immunity appears with risk of increasing IgG anti- T gondii concentration, which suggests a relapse of toxoplasmosis. Thus, in the context of immunodeficiency, routine quantification of Tg-IgG would alleviate the programmatic burden of this opportunistic infection in RLS with generalized HIV epidemics.

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Mechanisms of Human Innate Immune Evasion by Toxoplasma gondii

Cited by 131 publications

References 81 publications

In vitro Evaluation of Mannosylated Paromomycin-Loaded Solid Lipid Nanoparticles on Acute Toxoplasmosis

In vitro Evaluation of Mannosylated Paromomycin-Loaded Solid Lipid Nanoparticles on Acute Toxoplasmosis

The IL-33/ST2 Axis in Immune Responses Against Parasitic Disease: Potential Therapeutic Applications

High viremia and Poor Immunity are Potential Surrogates of Anti-toxoplasmic Immunoglobulin G Quantification among HIV-Infected Individuals: A Cross-sectional Study in Yaoundé, Cameroon

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