Recruitment of galectin-3 during cell invasion and intracellular trafficking of Trypanosoma cruzi extracellular amastigotes

Machado, Fabricio; Cruz, Leandro; Silva, Aline Alves da; Cruz, Mário Costa; Mortara, Renato Arruda; Roque-Barreira, Maria Cristina; Silva, Cláudio Vieira da

doi:10.1093/glycob/cwt097

Cited by 24 publications

(24 citation statements)

References 26 publications

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“…32 Gal-3 was implicated in the process of T. cruzi invasion. 33 Altogether, these data suggest that Gal-3 is involved in different aspects of the pathogenesis of CCC, from T. cruzi infection to immune response, inflammation, and tissue repair. Interestingly, a reduction of Gal-3 expression in the heart was observed accompanying decreased fibrosis and myocarditis after granulocyte colonystimulating factor treatment or cell therapy in chronically infected mice.…”

Section: Discussionmentioning

confidence: 84%

Association of Cardiac Galectin-3 Expression, Myocarditis, and Fibrosis in Chronic Chagas Disease Cardiomyopathy

Souza

Silva

Carvalho

et al. 2017

The American Journal of Pathology

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Chronic Chagas disease cardiomyopathy, caused by Trypanosoma cruzi infection, is a major cause of heart failure in Latin America. Galectin-3 (Gal-3) has been linked to cardiac remodeling and poor prognosis in heart failure of different etiologies. Herein, we investigated the involvement of Gal-3 in the disease pathogenesis and its role as a target for disease intervention. Gal-3 expression in mouse hearts was evaluated during T. cruzi infection by confocal microscopy and flow cytometry analysis, showing a high expression in macrophages, T cells, and fibroblasts. In vitro studies using Gal-3 knockdown in cardiac fibroblasts demonstrated that Gal-3 regulates cell survival, proliferation, and type I collagen synthesis. In vivo blockade of Gal-3 with N-acetyl-d-lactosamine in T. cruzi-infected mice led to a significant reduction of cardiac fibrosis and inflammation in the heart. Moreover, a modulation in the expression of proinflammatory genes in the heart was observed. Finally, histological analysis in human heart samples obtained from subjects with Chagas disease who underwent heart transplantation showed the expression of Gal-3 in areas of inflammation, similar to the mouse model. Our results indicate that Gal-3 plays a role in the pathogenesis of experimental chronic Chagas disease, favoring inflammation and fibrogenesis. Moreover, by demonstrating Gal-3 expression in human hearts, our finding reinforces that this protein could be a novel target for drug development for Chagas cardiomyopathy.

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Section: Discussionmentioning

confidence: 84%

Association of Cardiac Galectin-3 Expression, Myocarditis, and Fibrosis in Chronic Chagas Disease Cardiomyopathy

Souza

Silva

Carvalho

et al. 2017

The American Journal of Pathology

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“…To assess this, we analyzed galectin-3, a eukaryotic protein whose localization changes in response to the presence of damaged host membranes. Indeed, galectin-3 has been widely utilized to examine vacuolar integrity for other intracellular pathogens, such as Salmonella enterica serovar Typhimurium, Shigella flexneri , and Trypanosoma cruzi (62, 63). To begin, we infected a variety of macrophages with WT 130b for 16 h and examined galectin-3 localization by IFA.…”

Section: Resultsmentioning

confidence: 99%

Type II Secretion Substrates ofLegionella pneumophilaTranslocate Out of the Pathogen-Occupied Vacuole via a Semipermeable Membrane

Truchan

Christman

White

et al. 2017

mBio

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Legionella pneumophila replicates in macrophages in a host-derived phagosome, termed the Legionella-containing vacuole (LCV). While the translocation of type IV secretion (T4S) effectors into the macrophage cytosol is well established, the location of type II secretion (T2S) substrates in the infected host cell is unknown. Here, we show that the T2S substrate ProA, a metalloprotease, translocates into the cytosol of human macrophages, where it associates with the LCV membrane (LCVM). Translocation is detected as early as 10 h postinoculation (p.i.), which is approximately the midpoint of the intracellular life cycle. However, it is detected as early as 6 h p.i. if ProA is hyperexpressed, indicating that translocation depends on the timing of ProA expression and that any other factors necessary for translocation are in place by that time point. Translocation occurs with all L. pneumophila strains tested and in amoebae, natural hosts for L. pneumophila. It was absent in murine bone marrow-derived macrophages and murine macrophage cell lines. The ChiA chitinase also associated with the cytoplasmic face of the LCVM at 6 h p.i. and in a T2S-dependent manner. Galectin-3 and galectin-8, eukaryotic proteins whose localization is influenced by damage to host membranes, appeared within the LCV of infected human but not murine macrophages beginning at 6 h p.i. Thus, we hypothesize that ProA and ChiA are first secreted into the vacuolar lumen by the activity of the T2S and subsequently traffic into the macrophage cytosol via a novel mechanism that involves a semipermeable LCVM.

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“…For instance, galectin-3 accumulates on damaged bacterium-containing vesicles (93), notably including the LCV (94). Galectin-3 has been established as a marker for vacuole integrity during infection with S. enterica serovar Typhimurium, Shigella flexneri, and Trypanosoma cruzi (93,95). It was shown that the cytosolic galectin-8 also localizes to damaged vesicles and restricts Salmonella replication in HeLa cells (27).…”

Section: Discussionmentioning

confidence: 99%

A MicroRNA Network Controls Legionella pneumophila Replication in Human Macrophages via LGALS8 and MX1

Herkt

Caffrey

Surmann

et al. 2020

mBio

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Legionella pneumophila is an important cause of pneumonia. It invades alveolar macrophages and manipulates the immune response by interfering with signaling pathways and gene transcription to support its own replication. MicroRNAs (miRNAs) are critical posttranscriptional regulators of gene expression and are involved in defense against bacterial infections. Several pathogens have been shown to exploit the host miRNA machinery to their advantage. We therefore hypothesize that macrophage miRNAs exert positive or negative control over Legionella intracellular replication. We found significant regulation of 85 miRNAs in human macrophages upon L. pneumophila infection. Chromatin immunoprecipitation and sequencing revealed concordant changes of histone acetylation at the putative promoters. Interestingly, a trio of miRNAs (miR-125b, miR-221, and miR-579) was found to significantly affect intracellular L. pneumophila replication in a cooperative manner. Using proteome-analysis, we pinpointed this effect to a concerted downregulation of galectin-8 (LGALS8), DExD/H-box helicase 58 (DDX58), tumor protein P53 (TP53), and then MX dynamin-like GTPase 1 (MX1) by the three miRNAs. In summary, our results demonstrate a new miRNA-controlled immune network restricting Legionella replication in human macrophages. IMPORTANCE Cases of Legionella pneumophila pneumonia occur worldwide, with potentially fatal outcome. When causing human disease, Legionella injects a plethora of virulence factors to reprogram macrophages to circumvent immune defense and create a replication niche. By analyzing Legionella-induced changes in miRNA expression and genomewide chromatin modifications in primary human macrophages, we identified a cell-autonomous immune network restricting Legionella growth. This network comprises three miRNAs governing expression of the cytosolic RNA receptor DDX58/RIG-I, the tumor suppressor TP53, the antibacterial effector LGALS8, and MX1, which has been described as an antiviral factor. Our findings for the first time link TP53, LGALS8, DDX58, and MX1 in one miRNA-regulated network and integrate them into a functional node in the defense against L. pneumophila.

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Recruitment of galectin-3 during cell invasion and intracellular trafficking of Trypanosoma cruzi extracellular amastigotes

Cited by 24 publications

References 26 publications

Association of Cardiac Galectin-3 Expression, Myocarditis, and Fibrosis in Chronic Chagas Disease Cardiomyopathy

Association of Cardiac Galectin-3 Expression, Myocarditis, and Fibrosis in Chronic Chagas Disease Cardiomyopathy

Type II Secretion Substrates ofLegionella pneumophilaTranslocate Out of the Pathogen-Occupied Vacuole via a Semipermeable Membrane

A MicroRNA Network Controls Legionella pneumophila Replication in Human Macrophages via LGALS8 and MX1

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