Toxoplasma gondii Soluble Tachyzoite Antigen Triggers Protective Mechanisms against Fatal Intestinal Pathology in Oral Infection of C57BL/6 Mice

Benevides, Luciana; Cardoso, Cristina Ribeiro de Barros; Milanezi, Cristiane M.; Castro-Filice, Letícia S; Barenco, Paulo Victor Czarnewski; Sousa, Romulo Oliveira; Rodrigues, Raphael Silva; Mineo, José Roberto; Silva, João; Silva, Neide M.

doi:10.1371/journal.pone.0075138

Cited by 22 publications

(19 citation statements)

References 53 publications

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“…This reduction was also seen here in huCD2tg mice with toxoplasmosis. Not questioning the central role of IFNγ in infection control [ 8 ], little local and systemic IFNγ is a hallmark for protection from inflammation of the small intestine [ 25 ]. In IL-22-deficient mice, weak inflammation of the small intestine associates with low levels of the Th1 cytokine IL-18 [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Preventive anti-CD2 treatment does not impair parasite control in a murine toxoplasmosis model

Erben¹,

Pawlowski²,

Heimesaat³

et al. 2015

EuJMI

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Targeting human CD2 with the monoclonal antibody (mAb) CB.219 reduces intestinal inflammation in a colitis model where T cells carry human CD2. Here, we asked whether this mAb has adverse effects on infection control.Mice expressing human CD2 on T cells (huCD2tg) were orally infected with Toxoplasma (T.) gondii and treated with the human CD2-specific mAb CB.219 in a preventive setting. The intestinal T. gondii loads in CB.219 treated mice did not differ from the control group. Histologically, huCD2tg mice showed moderate ileal inflammation that did not change with CB.219 treatment. In the ileum, CB.219 treatment reduced the protein levels of interferon-γ, transforming growth factor β and interleukin-6, whereas interleukin-18 mRNA was slightly increased. The infiltration of neutrophils, macrophages, and T cells into the ileum was unaffected by CB.219 treatment. However, CB.219 treatment decreased the numbers of forkhead box P3+ regulatory T cells (Treg) in ileum and liver of huCD2tg mice. This was confirmed in vitro using human peripheral blood mononuclear cells.Taken together, targeting CD2+ T cells by the human CD2 mAb CB.219 does not prevent beneficial immune reactions necessary for pathogen control. Further experiments will address gut specificity, underlying mechanisms, and general applicability of CB.219 treatment.

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Section: Discussionmentioning

confidence: 99%

Preventive anti-CD2 treatment does not impair parasite control in a murine toxoplasmosis model

Erben¹,

Pawlowski²,

Heimesaat³

et al. 2015

EuJMI

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“…Inflammatory scores were represented as arbitrary units: 0–1, mild; 1–2, moderate; 2–3, severe; and >3, very severe; according to previously described protocol (48). Brain tissue samples from naïve mice served as negative controls.…”

Section: Methodsmentioning

confidence: 99%

Dectin-1 Compromises Innate Responses and Host Resistance against Neospora caninum Infection

et al. 2017

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Neospora caninum is an intracellular protozoan parasite that has drawn increasing interest due to its association with worldwide repetitive bovine abortions, which cause billionaire losses to the meat and dairy industries annually. Innate immunity plays an important role in infection control, and N. caninum activates the production of inflammatory mediators through toll-like receptors, NOD-like receptors, and mitogen-activated protein kinase signaling pathways. Advances in the knowledge of initial host–parasite interactions are desirable for the design of control measures against the infection, obliterating its pathogenesis. In that sense, we here aimed to describe the role of the innate C-type lectin receptor Dectin-1 during the infection by N. caninum. With that intent, we observed that the absence of Dectin-1, observed in genetically depleted (Dectin-1−/−) mice or competitively inhibited by an inert agonist [laminarin (LAM)], rescued 50% of the mice infected with lethal doses of N. caninum. Dectin-1−/− and LAM-treated mice also presented a reduction in the parasite load during acute and chronic phases, associated with decreased inflammatory scores in the central nervous system. Among all the cell phenotypes that migrated to the initial site of infection, dendritic cells and macrophages gained subpopulations with high Dectin-1 surface expression. The impairment of the receptor in these cells led to a decreased parasite burden, as well as augmented production of IL-12p40. We also found that Dectin-1+ cells produced less reactive oxygen species (ROS) at the initial site of the infection, while mice deficient in NADPH oxidase isoform 2 (NOX2−/−) were not able to control parasite replication and produce IL-12p40, even upon LAM treatment. Interestingly, the absence of functional Dectin-1 did not alter the susceptibility of mice against closely related Toxoplasma gondii. In conclusion, the gathered data suggest that Dectin-1 is involved in the parasite-induced downmodulation of ROS, and other key molecules triggered for the control of N. caninum infection and are a promising target for future development of protocols intended for intervention against neosporosis.

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“…It is being establish that T. gondii induces severe ileum inflammation by IFNγ high production and other mediators (LIESENFELD et al, 1996). As well as in the results presented in this study, a work developed by Benevides et al (2013) found that C57Bl/6 mice treated with STAg and subsequently infected with T. gondii exhibited lower tissue damage in the ileum compared to untreated animals. In addition, it was found that the IL-10 and IFNγ production was lower in these animals compared to the control group (PBS).…”

Section: Discussionsupporting

confidence: 69%

“…For this purpose, C57Bl/6 mice were treated with rNcROP4, STAg (soluble T. gondii antigens) and PBS. STAg was used due benefices results using this extract (BENEVIDES et al, 2013) in T. gondii-induced ileitis treatment.…”

Section: Treatment With Recombinant Rncrop4 Is Able To Reduce the T mentioning

confidence: 99%

Estimulação de vias inatas em células uterinas e ensaios de imunoprofilaxia em modelo murino visando o controle da neosporose bovina

Ramos¹

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Neospora caninum has caused great interest in the research due to its association with repeated abortion in the cattle herd, entailing billions of dollars of loss in livestock annually. Classified as a mandatory intracellular protozoan, vertical transmission is common in bovine hosts and the consequences generated will depend on the host immune response profile. In addition, N. caninum presents several secretory molecules important in the invasion process. Among them, NcROP4 is a rhoptry protein that has immunogenic character important for the process of invasion and evasion in the host cell. Here we aimed at two manuscripts to understand the innate mechanisms involved in the response against N. caninum in bovine uterine cells and to evaluate the immunomodulatory capacity of recombinant NcROP4 (rNcROP4) in the development of vaccine protocols and from there to test the immunotherapeutic protocols of an acute inflammatory pathology. The

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Toxoplasma gondii Soluble Tachyzoite Antigen Triggers Protective Mechanisms against Fatal Intestinal Pathology in Oral Infection of C57BL/6 Mice

Cited by 22 publications

References 53 publications

Preventive anti-CD2 treatment does not impair parasite control in a murine toxoplasmosis model

Preventive anti-CD2 treatment does not impair parasite control in a murine toxoplasmosis model

Dectin-1 Compromises Innate Responses and Host Resistance against Neospora caninum Infection

Estimulação de vias inatas em células uterinas e ensaios de imunoprofilaxia em modelo murino visando o controle da neosporose bovina

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