Antibody Repertoires Identify β-Tubulin as a Host Protective Parasite Antigen in Mice Infected With Trypanosoma cruzi

Montalvão, Fabricio; Nascimento, Daniel Ferreira do; Nunes, Marise P.; Koeller, Carolina M.; Morrot, Alexandre; Lery, Letícia Miranda Santos; Bisch, Paulo Mascarello; Teixeira, Santuza Maria Ribeiro; Vasconcellos, Ricardo José de Holanda; Freire-de-Lima, Leonardo; Lopes, Marcela F.; Heise, Norton; DosReis, George A.; Freire-de-Lima, Célio Geraldo

doi:10.3389/fimmu.2018.00671

Cited by 6 publications

(5 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Macrophages are crucial to the establishment of infection as a host cell and for the eradication of parasitism in the acute phase (Montalvao et al, 2018; Volpini et al, 2018). In order to evaluate the susceptibility of the macrophages from BALB/c or XID mice, we plated the macrophages and infected them with T. cruzi Dm 28c.…”

Section: Resultsmentioning

confidence: 99%

B-1 Cells May Drive Macrophages Susceptibility to Trypanosoma cruzi Infection

et al. 2019

View full text Add to dashboard Cite

B-1 cells can directly and indirectly influence the immune response. These cells are known to be excellent producers of natural antibodies and can secrete a variety of immunomodulatory molecules. They are also able to differentiate into B-1 cell-derived phagocytes (B-1CDP). B-1 cells can modulate macrophages to become less effective, and B-1CDP cells are more susceptible in infection models. In this work, we investigated the microbicidal ability of these cells in Trypanosoma cruzi infection in vitro. The results show that macrophages from BALB/c mice are more susceptible to infection than macrophages from XID mice. The resistance observed in macrophages from XID mice was abolished in the presence of B-1 cells, and this event seems to be associated with IL-10 production by B-1 cells, which may have contributed to the decrease of NO production. Additionally, B-1CDP cells were more permissive to intracellular T. cruzi infection than peritoneal macrophages. These findings strongly suggest that B-1 cells and B-1CDP cells have a potential role in the persistence of the parasite in host cells.

show abstract

Section: Resultsmentioning

confidence: 99%

B-1 Cells May Drive Macrophages Susceptibility to Trypanosoma cruzi Infection

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Immunized animals increased their specific IgG reactivity and were protected against T. cruzi infection. These results strongly suggest that proteomics, used for repertoire analysis, is a valid tool to identify protective antigens that could be vaccine candidates to protect against T. cruzi infection [84].…”

Section: Immune Responsementioning

confidence: 83%

Role of Proteomics in the Study of Trypanosoma cruzi Biology

Francisco¹,

Gutiérrez²,

González³

2019

Biology of Trypanosoma Cruzi

View full text Add to dashboard Cite

Proteomics is the science that studies the proteome, which corresponds to the global expression of proteins at a given time under determined conditions. In the last 20 years, proteomics has emerged as a powerful tool that has allowed the study of proteins that are expressed in the cell under normal or altered conditions as well as post-translational modifications, such as phosphorylation, glycosidation, acetylation, and methylation, among others. In this chapter, we present the main contributions of proteomics to the knowledge of Trypanosoma cruzi biology. Proteomes of all T. cruzi life cycle stages, secretomes/exoproteomes, post-translational modifications such as phosphorylation or acetylation and immunomes, interactomes, and glycomes are described. The role of proteomics in the identification of new chemotherapeutic targets and potential vaccine candidates will also be discussed.

show abstract

“…As shown, tubulin is abundantly represented among protist O -GlcNAcylated proteins and we found it on T. cruzi epimastigotes by immunoprecipitation as can be seen on Figure 1C; this was expected, since T. cruzi microtubules are cytoskeletal structures composed of two α- and one β-tubulin isoforms and are present in the flagellum and under the plasma membrane as subpellicular microtubules, and have important functions in motility, cellular morphology, intracellular transport, and cell division. Tubulin isoforms have also been studied as a target for substances with possible antichagasic activity (44) and as vaccine antigen candidates (45). Our results suggest the possibility to influence T. cruzi microtubule polymerization by interfering in tubulin O -GlcNAcylation, given the known role of O -GlcNAcylation in regulating microtubule formation (46).…”

Section: Discussionmentioning

confidence: 99%

Identification of O-Glcnacylated Proteins in Trypanosoma cruzi

et al. 2019

View full text Add to dashboard Cite

Originally an anthropozoonosis in the Americas, Chagas disease has spread from its previous borders through migration. It is caused by the protozoan Trypanosoma cruzi . Differences in disease severity have been attributed to a natural pleomorphism in T. cruzi . Several post-translational modifications (PTMs) have been studied in T. cruzi , but to date no work has focused on O-GlcNAcylation, a highly conserved monosaccharide-PTM of serine and threonine residues mainly found in nucleus, cytoplasm, and mitochondrion proteins. O-GlcNAcylation is thought to regulate protein function analogously to protein phosphorylation; indeed, crosstalk between both PTMs allows the cell to regulate its functions in response to nutrient levels and stress. Herein, we demonstrate O-GlcNAcylation in T. cruzi epimastigotes by three methods: by using specific antibodies against the modification in lysates and whole parasites, by click chemistry labeling, and by proteomics. In total, 1,271 putative O-GlcNAcylated proteins and six modification sequences were identified by mass spectrometry (data available via ProteomeXchange, ID PXD010285). Most of these proteins have structural and metabolic functions that are essential for parasite survival and evolution. Furthermore, O-GlcNAcylation pattern variations were observed by antibody detection under glucose deprivation and heat stress conditions, supporting their possible role in the adaptive response. Given the numerous biological processes in which O-GlcNAcylated proteins participate, its identification in T. cruzi proteins opens a new research field in the biology of Trypanosomatids, improve our understanding of infection processes and may allow us to identify new therapeutic targets.

show abstract

Antibody Repertoires Identify β-Tubulin as a Host Protective Parasite Antigen in Mice Infected With Trypanosoma cruzi

Cited by 6 publications

References 50 publications

B-1 Cells May Drive Macrophages Susceptibility to Trypanosoma cruzi Infection

B-1 Cells May Drive Macrophages Susceptibility to Trypanosoma cruzi Infection

Role of Proteomics in the Study of Trypanosoma cruzi Biology

Identification of O-Glcnacylated Proteins in Trypanosoma cruzi

Contact Info

Product

Resources

About