FIGURE 2 - uploaded by Nicholas C Smith
Content may be subject to copyright.
Activation of human monocytederived macrophages with ATP fails to affect the viability of T. gondii in the absence of functional P2X 7 R. A, P2RX7 haplotypes identified in NCCCTS samples after genotyping for seven SNPs; haplotype 1 is wild type at all seven SNP locations, haplotype 2 is homozygous for the non-loss-of-function SNPs at nt 1068 and 1772, and haplotype 3 is homozygous for the loss-of-function SNP at nt 1513. B, Intracellular T. gondii (RH) tachyzoite numbers were assessed in ATP-treated (3 mM) monocyte-derived macrophages from NCCCTS samples. The reduction in fluorescence of YFPlabeled T. gondii parasites measured by flow cytometry in ATP-treated cells was calculated at 24 h as a percentage of the untreated control for each subject. Results are the mean 6 SE, n = 3-6. There is a significantly lower percentage of parasites following ATP treatment in cells expressing functional P2X 7 R than in cells with the P2X 7 R 1513A.C loss-of-function SNP (p = 0.0015 using a general linear model, onefactor ANOVA with Tukey's post hoc test).
Source publication
The P2X7R is highly expressed on the macrophage cell surface, and activation of infected cells by extracellular ATP has been shown to kill intracellular bacteria and parasites. Furthermore, single nucleotide polymorphisms that decrease receptor function reduce the ability of human macrophages to kill Mycobacterium tuberculosis and are associated wi...
Contexts in source publication
Context 1
... of the NCCCTS cohort ( Fig. 2A) identified people with the most common loss-of-function polymorphism in P2RX7, the 1513A.C polymorphism (28), as well as those with wild-type P2RX7 or polymorphisms in linkage disequilibrium (1068G.A and 1772G.A) that do not reduce the function of the receptor (28). A reduction in parasite burden was observed following ATP treatment of ...
Context 2
... (28), as well as those with wild-type P2RX7 or polymorphisms in linkage disequilibrium (1068G.A and 1772G.A) that do not reduce the function of the receptor (28). A reduction in parasite burden was observed following ATP treatment of monocyte-derived macrophages from people with wild-type P2RX7 or with no loss-of-function polymorphisms (Fig. 2B). Conversely, ATP treatment of monocyte-derived macrophages cultured from people who are homozygous for the 1513A.C loss- of-function polymorphism had minimal effect on the number of intracellular T. gondii tachyzoites (Fig. ...
Context 3
... ATP treatment of monocyte-derived macrophages from people with wild-type P2RX7 or with no loss-of-function polymorphisms (Fig. 2B). Conversely, ATP treatment of monocyte-derived macrophages cultured from people who are homozygous for the 1513A.C loss- of-function polymorphism had minimal effect on the number of intracellular T. gondii tachyzoites (Fig. ...
Context 4
... of T. gondii RH strain tachyzoites. There was a trend toward higher serum NO levels in the P2X 7 R-deficient infected mice, although none of the differences achieved statistical signi- ficance; thus, control of T. gondii RH strain via the P2X 7 R is independent of NO production (Fig. 4). RAW 264.7 cells express functional P2X 7 R (Supplemental Fig. 2). Exposure to ATP induced rapid apoptosis of T. gondii-infected RAW 264.7 cells; more than 70% of cells were positive for annexin V by 1 h (Fig. 5A). At 5 h postexposure to ATP, a significant percentage (.30%) of apoptotic cells had progressed toward lysis (Fig. 5A). Similar levels of ATP-induced apoptosis and necrosis were seen in ...
Context 5
... that loss of viability of intracellular tachyzoites of T. gondii occurred in parallel to host cell apoptosis. Thus, 5 min post- exposure to ATP, almost all tachyzoites were stained green with acridine orange (Fig. 5B, panel 1) and, after 1 h, the parasites were still predominantly (73%) acridine orange positive and ethidium bromide negative (Fig. 5B, panel 2; Fig. 5C). However, by 2 h postexposure to ATP, 43% of the parasites were stained orange with ethidium bromide (Fig. 5B, panel 3; Fig. 5C). Meanwhile, tachyzoites exposed to ATP in cell-free media remained 100% viable, even after 2 h (data not shown). This demonstrates that a direct toxic effect of exogenous ATP on T. gondii is unlikely; ...
Context 6
... of known geno- types/haplotypes (20). We demonstrated that ATP-dependent killing of tachyzoites of T. gondii in vitro was virtually non- existent in people with the 1513A.C polymorphism, but readily observable in macrophages from people with wild-type receptors or in cells from people with polymorphisms that do not cause loss of receptor function (Fig. ...
Citations
... Conversely, macrophages in the resistant mouse strain secrete IL-1 and undergo pyroptosis (44). The inflammatory receptor P2X7R has been shown to be involved in NLRP activation leading to IL-1β secretion in T. gondii-infected mouse macrophages and human cells (51)(52)(53)(54)(55). In addition, NOD2 regulates T cell immune responses and plays a critical role in the host adaptive immune response to T. gondii (56). ...
Toxoplasma gondii is a pathogenic protozoan parasite of the Apicomplexa family that affects approximately 30% of the world's population. Symptoms are usually mild in immunocompetent hosts, but it can pose significant health risks to immunosuppressed patients and pregnant women. Current treatment options are limited, and new therapies and vaccines are needed. The innate immune system is the first to recognize T. gondii infection and activates pro-inflammatory cytokines and chemokines to promote acquired immunity. The IL-12/IFN-γ axis is particularly important, and when this pathway is inhibited, infection becomes uncontrolled and lethal. In mice, receptors such as Toll-like receptor 11 (TLR11), TLR12, and chemokine receptors are involved in T. gondii recognition and the modulation of immune responses. In humans, where TLR11 and TLR12 are absent, other mechanisms have been reported as the innate immune sensing system in T. gondii infection. Immune cells activated in response to infection produce IL-12, which stimulates the proliferation of natural killer cells and T cells and promotes the production of IFN-γ. Several IFN-γ-induced anti-T. gondii defense mechanisms inhibit parasite growth. These include nitric oxide production, indoleamine 2,3-dioxygenase, and the destruction of parasitophorous vacuoles by IFN-γ-inducible immunity related GTPase groups (IRGs and GBPs). Recent studies focusing on the diversity of IRGs in rodents and effector molecules in T. gondii suggest that host immune mechanisms and pathogen immune evasion mechanisms have co-evolved. Furthermore, it has been suggested that cysts are not simply dormant during chronic infection. This review summarizes recent findings on anti-T. gondii innate, adaptive, and cell-autonomous immune responses.
... Recently, the P2X7 receptor has been implicated in the immune response to T. gondii. P2X7 receptor-mediated killing of T. gondii is associated with phagolysosome formation that is not related to the generation of nitric oxide and is accompanied by host-cell apoptosis and the production of free oxygen radicals [15,16]. ...
... Two studies have demonstrated that ATP binding to P2RX7 triggers the fusion of lysosomes with the parasitophorous vacuole, resulting in the elimination of T. gondii tachyzoites in both murine and human macrophages [15,16]. Interestingly, a gain-of-function single-nucleotide polymorphism (SNP) in P2RX7 has been associated with resistance to both congenital and OT [19]. ...
Ocular toxoplasmosis (OT) is characterized by inflammation within the eye and is the most recognized clinical manifestation of toxoplasmosis. The objective of this study was to identify new single-nucleotide polymorphisms (SNPs) in the P2RX7 gene that may have significance in the immune response to OT in Colombian patients. A case-control study was conducted to investigate the associations between SNPs (rs1718119 and rs2230912) in the P2RX7 gene and OT in 64 Colombian patients with OT and 64 controls. Capillary electrophoresis was used to analyze the amplification products, and in silico algorithms were employed to predict deleterious SNPs. Stability analysis of amino acid changes indicated that both mutations could lead to decreased protein structure stability. A nonsynonymous SNP, Gln460Arg, located in the long cytoplasmic tail of the receptor, showed a significant association with OT (Bonferroni correction (BONF) = 0.029; odds ratio OR = 3.46; confidence interval CI: 1.05 to 11.39), while no significant association between rs1718119 and OT risk was observed. Based on the 3D structure analysis of the P2RX7 protein trimer, it is hypothesized that an increase in the flexibility of the cytoplasmic domain of this receptor could alter its function. This SNP could potentially serve as a biomarker for identifying Colombian patients at risk of OT.
... IFN-γ can activate macrophages and boost cytotoxic T cells, allowing them to eliminate intracellular parasites and infected cells. In more detail, IFN-γ exerts its anti-parasitic activity by increasing immunity-related GTPases (IRGs) and p65 guanylate-binding proteins (GBPs) to disrupt the parasitophorous vacuole [31], up-regulating indoleamine 2,3-dioxygenase for tryptophan depletion [32], producing nitric oxide (NO) by inducible NO synthase [33], activating P2X7 receptors [34], and increasing the release of oxygen radicals [35]. Furthermore, IFN-γ plays an important role in enhancing further IFN-γ production and additional cellular immune responses that favor pathogen killing and host protection via feedback mechanisms. ...
Toxoplasmosis and neosporosis are major protozoan diseases of global distribution. Toxoplasma gondii is the cause of toxoplasmosis, which affects almost all warm-blooded animals, including humans, while Neospora caninum induces neosporosis in many animal species, especially cattle. The current defective situation with control measures is hindering all efforts to overcome the health hazards and economic losses of toxoplasmosis and neosporosis. Adequate understanding of host-parasite interactions and host strategies to combat such infections can be exploited in establishing potent control measures, including vaccine development. Macrophages are the first defense line of innate immunity, which is responsible for the successful elimination of T.gondii or N. cani-num. This action is exerted via the immunoregulatory interleukin-12 (IL-12), which orchestrates the production of interferon gamma (IFN-γ) from various immune cells. Cellular immune response and IFN-γ production is the hallmark for successful vaccine candidates against both T. gondii and N. caninum. However, the discovery of potential vaccine candidates is a highly laborious, time-consuming and expensive procedure. In this review, we will try to exploit previous knowledge and our research experience to establish an efficient immunological approach for exploring potential vaccine candidates against T. gondii and N. caninum. Our previous studies on vaccine development against both T. gondii and N. caninum revealed a strong association between the successful and potential vaccine antigens and their ability to promote the macrophage secretion of IL-12 using a murine model. This phenomenon was emphasized using different recombinant antigens, parasites, and experimental approaches. Upon these data and research trials, IL-12 production from murine macrophages can be used as an initial predictor for judgment of vaccine efficacy before further evaluation in time-consuming and laborious in vivo experiments. However, more studies and research are required to conceptualize this immunological approach. 1. Overview There is a ''proof-of-concept" that vaccination is the cornerstone for the preventive and control strategies against numerous infectious diseases. In the case of endemic or pandemic situations, vaccination will be the optimal option for reducing hazards and resuming a normal lifestyle. Except for malaria, many protozoan infections are neglected, and the available information is extremely scanty not only for ordinary people but also for some members of the scientific community. Toxoplasma gondii (T. gondii) and Neospora caninum (N. caninum) are very similar protozoan parasites in many aspects of structure, biology, and pathogenesis. However, recent advances in research technologies have also Citation: Fereig, R.M.; Omar, M.A.; Alsayeqh, A.F. Exploiting the Macrophage Production of IL-12 in Improvement of Vaccine Development against Toxoplasma gondii and Neospora caninum Infections. Vaccines 2022, 10, 2082.
... ATP-induced IL-1β release in the whole blood from subjects harbouring the E496A SNP is lower than in subjects harbouring the wild type residue [137], suggesting that P2X7R loss-of-function SNPs may impair cytokine release by immune cells. The E496A polymorphism was associated with increased susceptibility to tuberculosis [138,139] and the less effective killing of other intracellular pathogens, such as Toxoplasma gondii [140]. In chronic Q fever, a persistent infection caused by the intracellular bacterium Coxiella burnetii [141], E496A may negatively affect the response to therapy [142]. ...
... Finally, the rs2305795 SNP in the 3 untranslated region of the P2RY11 gene was associated with narcolepsy [161]. An appraisal of the main disease-associated P2X7R SNPs is shown in Table 2. [139] Chronic Q fever [140,141] Graft-versus-host disease (GVHD) [146] Rheumatoid arthritis [151] rs1718119 1068 G > A A348T Gain ...
Extracellular ATP (eATP) and P2 receptors are novel emerging regulators of T-lymphocyte responses. Cellular ATP is released via multiple pathways and accumulates at sites of tissue damage and inflammation. P2 receptor expression and function are affected by numerous single nucleotide polymorphisms (SNPs) associated with diverse disease conditions. Stimulation by released nucleotides (purinergic signalling) modulates several T-lymphocyte functions, among which energy metabolism. Energy metabolism, whether oxidative or glycolytic, in turn deeply affects T-cell activation, differentiation and effector responses. Specific P2R subtypes, among which the P2X7 receptor (P2X7R), are either up- or down-regulated during T-cell activation and differentiation; thus, they can be considered indexes of activation/quiescence, reporters of T-cell metabolic status and, in principle, markers of immune-mediated disease conditions.
... Many studies have reported that T. gondii infection produces a significant amount of IL-1β in DCs, macrophages or monocytes but not in the intestinal epithelial lining (Lees et al., 2010;Witola et al., 2011;Cirelli et al., 2014;Gorfu et al., 2014;Ewald et al., 2014;Chu et al., 2017;Miller et al.,2015). T. gondii induces the activation of NLRP1 and NLRP3 in macrophages and DCs (Witola et al., 2011;Cirelli et al., 2014;Gorfu et al., 2014;Ewald et al., 2014). ...
... NLRP3 and the purinergic receptor P2X7R, which also leads to inflammasome activation, are widely expressed in rodents, humans and other animals. These receptors play an important role in the control of toxoplasmosis, as their deficiency or polymorphisms produce susceptibility to the disease(Corrêa et al., 2010;Lees et al., 2010; Gorfu et al., 2014) (Figure 2-4). ...
The study was conducted on 350 aborted women and 30 healthy women who have visited AL-Zahra maternity and paediatrics hospital in AL-Najaf province from November from August to January 2022. This study was designed to determine the effects of T. gondii infection on some parameters such as NLRP3, IL-18, IL-1β and TNF-α , The results showed a significant elevation (P<0.001) in serum concentration of The current study revealed that serum concentration of NLRP3 (ng/ml), IL-18 (pg/ml), IL-1β (pg/ml) and TNF-α (pg/ml) in patients infected with Toxoplasma gondii were significant increase (P (46. 21642 ± 0.524 ng/ml), (474. 12338± 0.906 pg/ml), (15. 41450± 0.218 pg/ml), (25. 4145065284± 0.218232 pg/ml) in compared to the control group (9.701792 ± 0.555 ng/ml), (97.107565 ± 0. 700 pg/ml), (4.129558 ± 0. 190 pg/ml), (6.45839 ± 0. 220 pg/ml). The current study has concluded that the infection with T. gondii affects the body's immunity by NLRP3, IL-18, IL-1β and TNF-α.
... In this sense, it was demonstrated that P2X7R activation inhibits T. gondii replication in macrophages by canonical NLRP3 inflammasome activation, which in turn produced IL-1β leading to increased mitochondrial ROS production [67]. These findings are consistent with other reports confirming that P2X7R activation in macrophages mediates the killing of tachyzoites [68,69]. Furthermore, P2X7R signaling in epithelial cells mediates CCL5 chemokine responses to promote the recruitment of CD11c + CD103 + dendritic cell in the intestinal epithelium promoting the initiation of the immune response [70]. ...
Infectious diseases are caused by the invasion of pathogenic microorganisms such as fungi, bacteria, viruses, and parasites. After infection, disease progression relies on the complex interplay between the host immune response and the microorganism evasion strategies. The host’s survival depends on its ability to mount an efficient protective anti-microbial response to accomplish pathogen clearance while simultaneously preventing tissue injury by keeping under control the excessive inflammatory process. The purinergic system has the dual function of regulating the immune response and triggering effector antimicrobial mechanisms. This review provides an overview of the current knowledge of the modulation of innate and adaptive immunity driven by the purinergic system during parasitic, bacterial and viral infections.
... 28 It is suggested that induced cell death of infected host macrophages via P2X7R activation is one of the recognized mechanisms for eradicating intracellular parasites. 29,30 In contrast, it is shown that several unknown mediators, including ATP, could elicit cell death in tumor-associated macrophages that subsequently favor tumor propagation and survival. 5 Taken together, these observations suggest that the extracellular ATP induces cell death in macrophages that could be beneficial or detrimental. ...
Purinergic receptors stimulation by adenosine triphosphate (ATP) contributes significantly to macrophage activation, and also macrophage cell death. Upon the macrophage activation, the protein load of the endoplasmic reticulum is increased which is resulted in the activation of unfolded protein response (UPR). In the current study, we aimed to evaluate the connection between prototypic P2X7 receptor agonist, extracellular 2ʹ(3ʹ)-O-(4-Benzoylbenzoyl)-ATP (BzATP), and the UPR pathway in macrophages.
The monocyte-derived macrophages from blood samples of 14 healthy volunteers were skewed toward M1 macrophages after incubation with LPS and IFN-γ. M1 macrophages were treated with 200 µM BzATP. The expression levels of UPR genes, including CHOP, HERP, GADD34, XBP1, and ATF6 in macrophages before and after treatment were measured using real-time polymerase chain reaction.
The results demonstrated that the expression of CHOP, HERP, and ATF6 is significantly decreased and the expression level of GADD34 and XBP1 is significantly increased after M1 polarization. BzATP not only significantly increased the expression levels of CHOP, GADD34, ATF6, and HERP but also significantly decreases the XBP1 expression level in M1 macrophages.
The present study showed that BzATP induces cellular stress in M1 macrophages by elevating the expression levels of UPR genes including CHOP, GADD34, ATF6, and reducing cell viability.
... It was found that the 1513C allele (coding for E486A; rs200141401) is a risk factor in the development of extrapulmonary and pulmonary tuberculosis in many ethnic populations [18,138,139]. Observation of low P2X7R function in subjects with symptomatic Toxoplasma gondii-infected human macrophages showed that the loss-of-function rs3751143 SNP (E496A) significantly reduced P2X7R-mediated parasite killing [140,141]. ...
Macrophages are mononuclear phagocytes which derive either from blood-borne monocytes or reside as resident macrophages in peripheral (Kupffer cells of the liver, marginal zone macrophages of the spleen, alveolar macrophages of the lung) and central tissue (microglia). They occur as M1 (pro-inflammatory; classic) or M2 (anti-inflammatory; alternatively activated) phenotypes. Macrophages possess P2X7 receptors (Rs) which respond to high concentrations of extracellular ATP under pathological conditions by allowing the non-selective fluxes of cations (Na+, Ca2+, K+). Activation of P2X7Rs by still higher concentrations of ATP, especially after repetitive agonist application, leads to the opening of membrane pores permeable to ~900 Da molecules. For this effect an interaction of the P2X7R with a range of other membrane channels (e.g., P2X4R, transient receptor potential A1 [TRPA1], pannexin-1 hemichannel, ANO6 chloride channel) is required. Macrophage-localized P2X7Rs have to be co-activated with the lipopolysaccharide-sensitive toll-like receptor 4 (TLR4) in order to induce the formation of the inflammasome 3 (NLRP3), which then activates the pro-interleukin-1β (pro-IL-1β)-degrading caspase-1 to lead to IL-1β release. Moreover, inflammatory diseases (e.g., rheumatoid arthritis, Crohn’s disease, sepsis, etc.) are generated downstream of the P2X7R-induced upregulation of intracellular second messengers (e.g., phospholipase A2, p38 mitogen-activated kinase, and rho G proteins). In conclusion, P2X7Rs at macrophages appear to be important targets to preserve immune homeostasis with possible therapeutic consequences.
... Early experiments showed that P2X7 activation potentiated killing of intracellular pathogens such as mycobacteria (Molloy et al., 1994), Chlamydia (Coutinho- Silva et al., 2003), Toxoplasma (Corrêa et al., 2010;Lees et al., 2010), and Leishmania (Chaves et al., 2009) mainly through facilitation of phagolysosome fusion and acceleration of acidification of parasitophorous vacuole, thus leading to the elimination of the microbial load (Morandini et al., 2014). A recent study by Salles et al. (2017) also demonstrated a key role of P2X7 in the response against the parasite Plasmodium chabaudi, showing that P2RX7 null mice are more susceptible to malaria infection due to altered Th1 differentiation. ...
... A recent study by Salles et al. (2017) also demonstrated a key role of P2X7 in the response against the parasite Plasmodium chabaudi, showing that P2RX7 null mice are more susceptible to malaria infection due to altered Th1 differentiation. Despite reports strongly suggesting that P2X7 is necessary for the development of cell-mediated acquired immunity for other infectious diseases (Corrêa et al., 2010;Lees et al., 2010;Salles et al., 2017), the type of immunity that is protective against M. leprae, there are no studies on the genetic association between leprosy and SNPs of P2RX7. In this work, we intend to fill this gap by investigating P2RX7 polymorphisms and P2X7 messenger RNA expression levels (in silico) in Brazilian leprosy patients. ...
... Similarly, macrophages from individuals with the rs3751143-C polymorphism are less effective in killing intracellular Toxoplasma gondii after exposure to ATP compared with macrophages of persons with reference allele rs3751143-A. Supporting a specific effect of P2X7 on T. gondii, macrophages from P2RX7 knockout mice are unable to kill T. gondii as effectively as wild-type mouse macrophages (Lees et al., 2010). This polymorphism was also associated with the development of chronic Q fever, which is a persistent infection, mostly of aortic aneurysms, vascular prostheses, or damaged heart valves, caused by the intracellular bacterium Coxiella burnetii (Jansen et al., 2019). ...
Leprosy is an infectious disease still highly prevalent in Brazil, having been detected around 27,863 new cases in 2019. Exposure to Mycobacterium leprae may not be sufficient to trigger the disease, which seems to be influenced by host immunogenetics to determine resistance or susceptibility. The purinergic receptor P2X7 plays a crucial role in immunity, inflammation, neurological function, bone homeostasis, and neoplasia and is associated with several infectious and non-infectious diseases. Here, we first compare the P2RX7 expression in RNA-seq experiments from 16 leprosy cases and 16 healthy controls to establish the magnitude of allele-specific expression for single-nucleotide polymorphisms of the gene P2RX7 and to determine the level of gene expression in healthy and diseased skin. In addition, we also evaluated the association of two P2RX7 single-nucleotide polymorphisms (c.1513A>C/rs3751143 and c.1068A>G/rs1718119) with leprosy risk. The expression of P2RX7 was found significantly upregulated at macrophage cells from leprosy patients compared with healthy controls, mainly in macrophages from lepromatous patients. Significant risk for leprosy disease was associated with loss function of rs3751143 homozygous mutant CC [CC vs. AA: p = 0.001; odds ratio (OR) = 1.676, 95% CI = 1.251–2.247] but not with heterozygous AC (AC vs. AA: p = 0.001; OR = 1.429, 95% CI = 1.260–1.621). Contrary, the polymorphic A allele from the gain function of rs1718119 was associated with protection for the development of leprosy, as observed in the dominant model (AA + AG × GG p = 0.0028; OR = 0.03516; CI = 0.1801–0.6864). So, our results suggest that the functional P2X7 purinergic receptor may exert a key role in the Mycobacterium death inside macrophages and inflammatory response, which is necessary to control the disease.
... Relevant to toxoplasmosis, this process engages the adapter protein apoptosisassociated speck-like protein containing a CARD (ASC), which results in caspase-1-mediated processing of IL-1α, IL-1β, and IL-18 to their bioactive forms, but can also lead to pyroptosis, a form of inflammatory cell death (Snyder and Oberst, 2021). Genomewide association studies linked single nucleotide polymorphisms in the N-terminus of NLRP1 with susceptibility to congenital toxoplasmosis (Witola et al., 2011) and the NLRP3 inflammasome activator P2X7R with clinical toxoplasmosis in immunocompetent patients (Lees et al., 2010). In contrast, polymorphisms in the NLRP1 locus of Lewis rats are associated with enhanced death of cells infected in vitro and increased resistance to T. gondii in vivo (Cavaillès et al., 2006;Cirelli et al., 2014). ...
... Other examples revolve around the IL-1 family, as exemplified by P2X7R, the purinergic receptor for ATP that mediates cellular depolarization and inflammasome activation associated with cell death, IL-1 processing, and ROS production. P2X7R has been linked to intracellular killing of T. gondii (Lees et al., 2010); to the ability of T. gondii to promote epithelial cell production of CCL5, TNF, and IL-6 ; and to NLRP3 inflammasome activation in human epithelial cells and mouse macrophages (Moreira-Souza et al., 2017;Quan et al., 2018). Likewise, ISG15 is an unconventional secreted alarmin (Perng and Lenschow, 2018), and its release at the site of infection contributes to the recruitment of DCs that produce IL-1β and enhance local production of IFN-γ (Napolitano et al., 2018). ...
The intracellular parasite Toxoplasma gondii has long provided a tractable experimental system to investigate how the immune system deals with intracellular infections. This review highlights the advances in defining how this organism was first detected and the studies with T. gondii that contribute to our understanding of how the cytokine IFN-γ promotes control of vacuolar pathogens. In addition, the genetic tractability of this eukaryote organism has provided the foundation for studies into the diverse strategies that pathogens use to evade antimicrobial responses and now provides the opportunity to study the basis for latency. Thus, T. gondii remains a clinically relevant organism whose evolving interactions with the host immune system continue to teach lessons broadly relevant to host-pathogen interactions.
