AFAP-1L1-mediated actin filaments crosslinks hinder Trypanosoma cruzi cell invasion and intracellular multiplication

Araújo, Karine Canuto Loureiro de; Teixeira, Thaíse Lara; Machado, Fabricio; Silva, Aline Alves da; Quintal, Amanda Pífano Neto; Silva, Cláudio Vieira da

doi:10.1016/j.actatropica.2016.06.028

Cited by 6 publications

(5 citation statements)

References 19 publications

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Section: Resultssupporting

confidence: 52%

“…The importance of actin cytoskeleton during parasite replication has been previously demonstrated by other authors (24)(25)(26). AFAP-1L1 knockout cells, which showed lower actin polymerization, were found to have higher intracellular replication rate of strain T. cruzi (26). Previous studies have reported that a more rigid cytoskeleton retains the parasite within the host cell (24), while its disarrangement would be more conducive to the free intracellular replication of T. cruzi (25).…”

Section: Resultsmentioning

confidence: 61%

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The Recombinant Form of Trypanosoma cruzi P21 Controls Infection by Modulating Host Immune Response

Martins

Santos

et al. 2020

Front. Immunol.

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Trypanosoma cruzi P21 protein (P21) is a putative secreted and immunomodulatory molecule with potent bioactive properties such as induction of phagocytosis and actin cytoskeleton polymerization. Despite the bioactive properties described so far, the action of P21 on parasite replication in muscle cell lineage or T. cruzi parasitism during acute experimental infection is unclear. We observed that recombinant P21 (rP21) decreased the multiplication of T. cruzi in C2C12 myoblasts, phenomenon associated with greater actin polymerization and IFN-γ and IL-4 higher expression. During experimental infection, lower cardiac nests, inflammatory infiltrate and fibrosis were observed in mice infected and treated with rP21. These results were correlated with large expression of IFN-γ counterbalanced by high levels of IL-10, which was consistent with the lower cardiac tissue injury found in these mice. We have also observed that upon stress, such as that induced by the presence of the IFN-γ cytokine, T. cruzi produced more P21. The effect of P21 in controlling the replication of T. cruzi, may indicate an evolutionary mechanism of survival developed by the parasite. Thus, when subjected to different stress conditions, the protozoan produces more P21, which induces T. cruzi latency in the host organism, enabling the protozoan to evade the host's immune system.

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Section: Resultssupporting

confidence: 52%

Section: Resultsmentioning

confidence: 61%

The Recombinant Form of Trypanosoma cruzi P21 Controls Infection by Modulating Host Immune Response

Martins

Santos

et al. 2020

Front. Immunol.

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“…After shRNA transduction cells were analyzed by flow cytometry to check the knocking down expression of Gal-3. Transduction and expression analysis were performed as described by Araújo et al ( 2016 ) WT, control knockdown (CTRL KD) and Gal-3 KD cells were used.…”

Section: Methodsmentioning

confidence: 99%

Galectin-3: A Friend but Not a Foe during Trypanosoma cruzi Experimental Infection

Silva

Teixeira

et al. 2017

Front. Cell. Infect. Microbiol.

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Trypanosoma cruzi interacts with host cells, including cardiomyocytes, and induces the production of cytokines, chemokines, metalloproteinases, and glycan-binding proteins. Among the glycan-binding proteins is Galectin-3 (Gal-3), which is upregulated after T. cruzi infection. Gal-3 is a member of the lectin family with affinity for β-galactose containing molecules; it can be found in both the nucleus and the cytoplasm and can be either membrane-associated or secreted. This lectin is involved in several immunoregulatory and parasite infection process. Here, we explored the consequences of Gal-3 deficiency during acute and chronic T. cruzi experimental infection. Our results demonstrated that lack of Gal-3 enhanced in vitro replication of intracellular parasites, increased in vivo systemic parasitaemia, and reduced leukocyte recruitment. Moreover, we observed decreased secretion of pro-inflammatory cytokines in spleen and heart of infected Gal-3 knockout mice. Lack of Gal-3 also led to elevated mast cell recruitment and fibrosis of heart tissue. In conclusion, galectin-3 expression plays a pivotal role in controlling T. cruzi infection, preventing heart damage and fibrosis.

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“…Cell culture and parasite maintenance -Immortalised macrophages (macrophages C57) were derived from the bone marrow of C57BL/6 mice and maintained according to Araujo et al (37) L. (L.) amazonensis promastigotes (IFLA/BR/67/PH8) were maintained in Brain Heart Infusion -HiMedia medium supplemented with 10% foetal bovine serum (FBS) (Cultilab, Campinas, Brazil), 100 mg of gentamicin/mL and 2 mM Lglutamine (GibcoBRL, Life Technologies, New York) at 23ºC. Promastigotes in the stationary phase (metacyclic) were used in the experiments.…”

Section: Crotalus Durissus Collilineatus Serum and Bothropsmentioning

confidence: 99%

“…For both protocols, cells were fixed with Bouin's solution (HT10132 Sigma Aldrich) and stained with Giemsa (1:20 -P3288 Sigma Aldrich). (37) Finally, the coverslips were analysed under a light microscope to assess the following parameters: number of cells with invaded parasites (invasion rate) and total number of parasites invaded to these cells in a total of 200 cells examined randomly. Three independent experiments were performed in triplicate for each treatment.…”

Section: Cellular Viability In Promastigote Forms Of L (L)mentioning

confidence: 99%

Antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, on Leishmania (Leishmania) amazonensis

Gonçalves,

Lopes,

Teixeira

et al. 2023

Mem. Inst. Oswaldo Cruz

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BACKGROUND Leishmaniasis, a neglected disease caused by the parasite Leishmania, is treated with drugs associated with high toxicity and limited efficacy, in addition to constant reports of the emergence of resistant parasites. In this context, snake serums emerge as good candidates since they are natural sources with the potential to yield novel drugs.OBJECTIVES We aimed to show the antileishmanial effects of γCdcPLI, a phospholipase A 2 inhibitor from Crotalus durissus collilineatus snake serum, against Leishmania (Leishmania) amazonensis.METHODS Promastigotes forms were exposed to γCdcPLI, and we assessed the parasite viability and cell cycle, as well as invasion and proliferation assays.FINDINGS Despite the low cytotoxicity effect on macrophages, our data indicate that γCdcPLI has a direct effect on parasites promoting an arrest in the G1 phase and reduction in the G2/M phase at the highest dose tested. Moreover, this PLA 2 inhibitor reduced the parasite infectivity when promastigotes were pre-treated. Also, we demonstrated that the γCdcPLI treatment modulated the host cell environment impairing early and late steps of the parasitism.MAIN CONCLUSIONS γCdcPLI is an interesting tool for the discovery of new essential targets on the parasite, as well as an alternative compound to improve the effectiveness of the leishmaniasis treatment.

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AFAP-1L1-mediated actin filaments crosslinks hinder Trypanosoma cruzi cell invasion and intracellular multiplication

Cited by 6 publications

References 19 publications

The Recombinant Form of Trypanosoma cruzi P21 Controls Infection by Modulating Host Immune Response

The Recombinant Form of Trypanosoma cruzi P21 Controls Infection by Modulating Host Immune Response

Galectin-3: A Friend but Not a Foe during Trypanosoma cruzi Experimental Infection

Antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, on Leishmania (Leishmania) amazonensis

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