An Overview of Peripheral Blood Mononuclear Cells as a Model for Immunological Research of Toxoplasma gondii and Other Apicomplexan Parasites

Dávila, John Alejandro Acosta; Rios, Alejandro Hernandez De Los

doi:10.3389/fcimb.2019.00024

Cited by 38 publications

(19 citation statements)

References 78 publications

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“…However, we did not find any difference in the secretion of this cytokine between groups. One possible explanation lies in the fact that in our previous studies we used total lysate antigen to stimulate PBMCs, but because T. gondii release proteins that are involved in the parasite's immune evasion mechanisms in a highly regulated manner (Tosh et al, 2016), the use of live parasites is recommended for this type of immunological experiments (Acosta Davila and Hernandez De Los Rios, 2019).…”

Section: Discussionmentioning

confidence: 99%

Influence of Two Major Toxoplasma Gondii Virulence Factors (ROP16 and ROP18) on the Immune Response of Peripheral Blood Mononuclear Cells to Human Toxoplasmosis Infection

Hernández-de-los-Ríos

Murillo-León

Mantilla-Muriel

et al. 2019

Front. Cell. Infect. Microbiol.

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Toxoplasma gondii ROP16 and ROP18 proteins have been identified as important virulence factors for this parasite. Here, we describe the effect of ROP16 and ROP18 proteins on peripheral blood mononuclear cells (PBMCs) from individuals with different clinical status of infection. We evaluated IFN-γ, IL-10, and IL-1β levels in supernatants from PBMCs cultures infected with tachyzoites of the T. gondii wild-type RH strain or with knock-out mutants of the rop16 and rop18 encoding genes (RHΔrop16 and RHΔrop18). Cytokine secretion was compared between PBMCs obtained from seronegative individuals (n = 10), with those with chronic asymptomatic (n = 8), or ocular infection (n = 12). We also evaluated if polymorphisms in the genes encoding for IFN-γ, IL-10, IL-1β, Toll-like receptor 9 (TLR9), and purinoreceptor P2RX7 influenced the production of the encoded proteins after ex vivo stimulation. In individuals with chronic asymptomatic infection, only a moderate effect on IL-10 levels was observed when PBMCs were infected with RHΔrop16, whereas a significant difference in the levels of inflammatory cytokines IFN-γ and IL-1β was observed in seronegative individuals, but this was also dependent on the host's cytokine gene polymorphisms. Infection with ROP16-deficient parasites had a significant effect on IFN-γ production in previously non-infected individuals, suggesting that ROP16 which is considered as a virulence factor plays a role during the primary infection in humans, but not in the secondary immune response.

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Section: Discussionmentioning

confidence: 99%

Influence of Two Major Toxoplasma Gondii Virulence Factors (ROP16 and ROP18) on the Immune Response of Peripheral Blood Mononuclear Cells to Human Toxoplasmosis Infection

Hernández-de-los-Ríos

Murillo-León

Mantilla-Muriel

et al. 2019

Front. Cell. Infect. Microbiol.

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“…For human blood mononuclear cells (PBMC) studies, healthy donors (n = 3) with no clinical history were selected to donate blood under authorized supervision from subjects who had given their consent. PBMCs are blood cells with a heterogeneous cell population, comprising of monocytes, lymphocytes, and macrophages [71,72]. PBMCs were separated in a single-step density centrifugation technique, as described previously [14].…”

Section: Pbmc Cell Culture Fucoidan Treatment and Stimulationmentioning

confidence: 99%

Anti-Inflammatory Activity of Fucoidan Extracts In Vitro

et al. 2021

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Fucoidans are sulfated, complex, fucose-rich polymers found in brown seaweeds. Fucoidans have been shown to have multiple bioactivities, including anti-inflammatory effects, and are known to inhibit inflammatory processes via a number of pathways such as selectin blockade and enzyme inhibition, and have demonstrated inhibition of inflammatory pathologies in vivo. In this current investigation, fucoidan extracts from Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica were assessed for modulation of pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-6) by human peripheral blood mononuclear cells (PBMCs) and in a human macrophage line (THP-1). Fucoidan extracts exhibited no signs of cytotoxicity in THP-1 cells after incubation of 48 h. Additionally, all fucoidan extracts reduced cytokine production in LPS stimulated PBMCs and human THP-1 cells in a dose-dependent fashion. Notably, the 5–30 kDa subfraction from Macrocystis pyrifera was a highly effective inhibitor at lower concentrations. Fucoidan extracts from all species had significant anti-inflammatory effects, but the lowest molecular weight subfractions had maximal effects at low concentrations. These observations on various fucoidan extracts offer insight into strategies that improve their efficacy against inflammation-related pathology. Further studies should be conducted to elucidate the mechanism of action of these extracts.

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“…On the other hand, Safronova et al [18] did not observe any IL12/IL23p40 secretion from PBMCs infected with type II Toxoplasma. This discrepancy could be due to differences in the isolation and purification of monocytes, time point of the assay and, most importantly, the multiplicity of infection (MOI) [71].…”

Section: Plos Pathogensmentioning

confidence: 99%

Toxoplasma GRA15 and GRA24 are important activators of the host innate immune response in the absence of TLR11

2020

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The murine innate immune response against Toxoplasma gondii is predominated by the interaction of TLR11/12 with Toxoplasma profilin. However, mice lacking Tlr11 or humans, who do not have functional TLR11 or TLR12, still elicit a strong innate immune response upon Toxoplasma infection. The parasite factors that determine this immune response are largely unknown. Herein, we investigated two dense granule proteins (GRAs) secreted by Toxoplasma, GRA15 and GRA24, for their role in stimulating the innate immune response in Tlr11 -/mice and in human cells, which naturally lack TLR11/TLR12. Our results show that GRA15 and GRA24 synergistically shape the early immune response and parasite virulence in Tlr11 -/mice, with GRA15 as the predominant effector. Nevertheless, acute virulence in Tlr11 -/mice is still dominated by allelic combinations of ROP18 and ROP5, which are effectors that determine evasion of the immunity-related GTPases. In human macrophages, GRA15 and GRA24 play a major role in the induction of IL12, IL18 and IL1β secretion. We further show that GRA15/GRA24-mediated IL12, IL18 and IL1β secretion activates IFNγ secretion by peripheral blood mononuclear cells (PBMCs), which controls Toxoplasma proliferation. Taken together, our study demonstrates the important role of GRA15 and GRA24 in activating the innate immune response in hosts lacking TLR11.

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An Overview of Peripheral Blood Mononuclear Cells as a Model for Immunological Research of Toxoplasma gondii and Other Apicomplexan Parasites

Cited by 38 publications

References 78 publications

Influence of Two Major Toxoplasma Gondii Virulence Factors (ROP16 and ROP18) on the Immune Response of Peripheral Blood Mononuclear Cells to Human Toxoplasmosis Infection

Influence of Two Major Toxoplasma Gondii Virulence Factors (ROP16 and ROP18) on the Immune Response of Peripheral Blood Mononuclear Cells to Human Toxoplasmosis Infection

Anti-Inflammatory Activity of Fucoidan Extracts In Vitro

Toxoplasma GRA15 and GRA24 are important activators of the host innate immune response in the absence of TLR11

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