Increased resistance to the first-line treatment against P. falciparum malaria, artemisinin-based combination therapies, has been reported. Here, we tested the effect of crude ethanolic extract of the fungus Trichoderma stromaticum (Ext-Ts) on the growth of P. falciparum NF54 in infected human red blood cells (ihRBCs) and its anti-malarial and anti-inflammatory properties in a mouse model of experimental cerebral malaria. For this purpose, ihRBCs were treated with Ext-Ts and analysed for parasitaemia; C57BL/6 mice were infected with P. berghei ANKA (PbA), treated daily with Ext-Ts, and clinical, biochemical, histological and immunological features of the disease were monitored. It was observed that Ext-Ts presented a dose-dependent ability to control P. falciparum in ihRBCs. In addition, it was demonstrated that Ext-Ts treatment of PbA-infected mice was able to increase survival, prevent neurological signs and decrease parasitaemia at the beginning of infection. These effects were associated with systemically decreased levels of lipids and IFN-γ, ICAM-1, VCAM-1 and CCR5 cerebral expression, preserving blood brain barrier integrity and attenuating the inflammatory lesions in the brain, liver and lungs. These results suggest that Ext-Ts could be a source of immunomodulatory and antimalarial compounds that could improve the treatment of cerebral malaria.
Background
Toxoplasma gondii is a protozoan with worldwide distribution and triggers a strong Th1 immune response in infected susceptible hosts. On the contrary, most helminth infections are characterized by Th2 immune response and the use of helminth‐derived antigens to regulate immune response in inflammatory disorders has been broadly investigated.
Objectives
The aim of this study was to investigate whether treatment with Strongyloides venezuelensis antigen extract (SvAg) would alter immune response against T gondii.
Methods
C57BL/6 mice were orally infected with T gondii and treated with SvAg, and parasitological, histological and immunological parameters were investigated.
Results
It was observed that SvAg treatment improved survival rates of T gondii‐infected mice. At day 7 post‐infection, the parasite load was lower in the lung and small intestine of infected SvAg‐treated mice than untreated infected mice. Remarkably, SvAg‐treated mice infected with T gondii presented reduced inflammatory lesions in the small intestine than infected untreated mice and decreased intestinal and systemic levels of IFN‐γ, TNF‐α and IL‐6. In contrast, SvAg treatment increased T gondii‐specific IgA serum levels in infected mice.
Conclusions
S venezuelensis antigen extract has anti‐parasitic and anti‐inflammatory properties during T gondii infection suggesting as a possible alternative to parasite and inflammation control.
5-Lipoxygenase (5-LO) is an enzyme required for the production of leukotrienes and lipoxins and interferes with parasitic infections.
In vitro
,
Toxoplasma gondii
inhibits leukotriene B
4
(LTB
4
) production, and mice deficient in 5-LO are highly susceptible to infection. The aim of this study was to investigate the effects of the pharmacological inhibition of the 5-LO pathway and exogenous LTB
4
supplementation during experimental toxoplasmosis.
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