Daniela Ferreira Chame

Universidade Federal de Minas Gerais

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Glória Regina Franco

Universidade Federal de Minas Gerais

Carlos Renato Machado

Universidade Federal de Minas Gerais

Daniela de Laet Souza

Universidade Federal de Minas Gerais

Andréa Mara Macedo

Universidade Federal de Minas Gerais

Egler Chiari

Universidade Federal de Minas Gerais

E. B. Tahara

Universidade Federal de Minas Gerais

Helaine Graziele Santos Vieira

Garvan Institute of Medical Research

NE Toledo

Universidade Federal de Minas Gerais

Erich Birelli Tahara

Universidade Federal de Minas Gerais

Raphael Pavani

National Human Genome Research Institute

Cooperative Institutions

Universidade Federal de Minas Gerais

Fundação Oswaldo Cruz

Universidade de São Paulo

Durham University

Instituto Butantan

Consejo Nacional de Investigaciones Científicas y Técnicas

Universidade Estadual de Campinas (UNICAMP)

Instituto Nacional do Câncer

Universidade Estadual Paulista (Unesp)

Umeå University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Differential modulation of mouse heart gene expression by infection with twoTrypanosoma cruzistrains: a transcriptome analysis

bioRxiv (Cold Spring Harbor Laboratory) (2019)

TBR Castro MCC Canesso Mariana Boroni Daniela Ferreira Chame Daniela de Laet Souza

The protozoan Trypanosoma cruzi ( T. cruzi ) is a well-adapted parasite to mammalian hosts and the pathogen of Chagas disease in humans. As both host and T. cruzi are highly genetically diverse, many variables come into play during infection, making disease outcomes difficult to predict. One important challenge in the field of Chagas disease research is determining the main factors leading to parasite establishment in the chronic stage in some organs, mainly the heart and/or digestive system. Our group previously showed that distinct strains of T. cruzi (JG and Col1.7G2) acquired differential tissue distribution in the chronic stage in dually-infected BALB/c mice. To investigate changes in the host triggered by the two distinct T. cruzi strains, we assessed the gene expression profile of BALB/c mouse hearts infected with either JG, Col1.7G2 or an equivalent mixture of both parasites during the initial phase of infection. This study demonstrates a clear distinction in host gene expression modulation by both parasites. Col1.7G2 strongly activated Th1-polarized immune signature genes, whereas JG showed only minor activation of the host immune response. Moreover, JG strongly reduced the expression of genes for ribosomal proteins and mitochondrial proteins related to the electron transport chain. Interestingly, evaluation of gene expression in mice inoculated with the mixture of parasites showed expression profiles for both up- and down-regulated genes, indicating the coexistence of both parasite strains in the heart during the acute phase. This study suggests that different strains of T. cruzi may be distinguished by their efficiency in activating the immune system, modulating host energy and reactive oxygen species production and decreasing protein synthesis during early infection, which may be crucial in defining parasite persistence in specific organs. Author Summary The causative agent of Chagas disease, Trypanosoma cruzi , retains high genetic diversity, and its populations vary greatly across geographic locations. The T. cruzi mammalian hosts, including humans, also have high genetic variation, making it difficult to predict the disease outcome. Accordingly, this variability must be taken into account in several studies aiming to interrogate the effect of polyparasitism in drug trials, vaccines, diagnosis or basic research. Therefore, there is a growing need to consider the interaction between the pathogen and the host immune system in mixed infections. In the present work, we present an in-depth analysis of the gene expression of hearts from BALB/c mice infected with Col1.7G2 and JG alone or a mixture of both strains. Col1.7G2 induced a higher Th1 inflammatory response, while JG exhibited a weaker activation of immune response genes. Furthermore, JG-infected mice showed a notable reduction in the expression of genes responsible for mitochondrial oxidative phosphorylation and protein synthesis. Interestingly, the mixture-infected group displayed changes in gene expression as caused by both strains. Overall, we provided new insights into the host-pathogen interaction in the context of single and dual infection, showing remarkable differences in host gene expression modulation by two T. cruzi strains.

Chagas Disease

10.1101/574343

Cite

Citations (1)

Trypanosoma cruzi RNA-binding protein ALBA30 aggregates into cytoplasmic foci under nutritional stress

Parasitology Research (2020)

Daniela Ferreira Chame Daniela de Laet Souza Helaine Graziele Santos Vieira Erich Birelli Tahara Andréa Mara Macedo

Stress granule

10.1007/s00436-019-06554-w

Cite

Citations (4)

Trypanosoma cruzi RNA-binding protein DRBD3: perinuclear foci formation during benznidazole exposure

Anais da Academia Brasileira de Ciências (2024)

Daniela Ferreira Chame DANIELA DE LAET-SOUZA Helaine Graziele Santos Vieira E. B. Tahara Andréa Mara Macedo

Benznidazole (BZ) is the trypanocidal compound of choice for Chagas disease, a neglected tropical disease in the Americas. However, this drug often fails to cure the infection. The regulation of gene expression in Trypanosoma cruzi, the causative agent of Chagas disease, is based on post-transcriptional mechanisms. When environmental changes cause translational arrest, RNA-binding proteins, and their target mRNAs assemble into cytoplasmic bodies, known as RNA granules, which act as RNA sorting centers. We have characterized the T. cruzi RNA-binding protein DRBD3, which has two RRMs domains, and a C-terminal low-complexity sequence rich in proline and glutamines. Using a tagged form of TcDRBD3 (rTcDRBD3), we showed that this protein resides in the cytoplasm, but localizes into perinuclear cytoplasmic foci after BZ exposure. RNA staining after BZ also showed that this molecule accumulates into perinuclear cytoplasmic foci. Moreover, BZ and puromycin treatment enhanced the colocalization of rTcDRBD3 and RNA, suggesting that TcDRBD3 granules repertoire harbors RNAs released from polysomes. Under starvation, rTcDRBD3 granules localized throughout the cytoplasm and also increased in number in the presence of puromycin. Our results suggest that TcDRBD3 accumulates into perinuclear granules that harbor RNA and also that its localization varies according to the type of stress.

Benznidazole

10.1590/0001-3765202420240321

Cite

Citations (0)

Differential Modulation of Mouse Heart Gene Expression by Infection With Two Trypanosoma cruzi Strains: A Transcriptome Analysis

Frontiers in Genetics (2020)

Tiago B. R. Castro Maria Cecília Campos Canesso Mariana Boroni Daniela Ferreira Chame Daniela de Laet Souza

Chagas Disease

10.3389/fgene.2020.01031

Cite

Citations (12)

DNA lesions that block transcription induce the death of Trypanosoma cruzi via ATR activation, which is dependent on the presence of R-loops

DNA repair (2024)

I.C. Mendes Willian dos Reis Bertoldo Adalberto Sales Miranda-Junior Antônio Vinícius de Assis Bruno Marçal Repolês

Transcription

RNA polymerase II

10.1016/j.dnarep.2024.103726

Cite

Citations (0)

TLR 9 involvement in early protection induced by immunization with rPb27 against Paracoccidioidomycosis

Microbes and Infection (2015)

Elis Araujo Morais Daniela Ferreira Chame Eliza Mathias Melo Junnia Alvarenga de Carvalho Oliveira Ana Paula

Paracoccidioidomycosis is caused by fungi of the Paracoccidioides genus and constitutes the most prevalent deep mycosis in Latin America. Toll-like receptors promote immune response against infectious agents. Recently, it was reported that TLR9 is crucial for mice survival during the first 48 h of P. brasiliensis infection. In this study, we used CPG oligodeoxynucleotide motif as an adjuvant with and without rPb27 to immunize mice against Paracoccidioidomycosis. CPG adjuvant induced differential recruitment of lymphocytes in the inflammatory process and a lower recruitment of neutrophils. In addition, CPG induced the production of pro-inflammatory cytokines such as IL-1β, TNF-α, IL-6 and IL-12; increased phagocytic ability and microbicidal activity by macrophages; and induced differential production of lgG2a and lgG2b, subtypes of Ig. Knockout mice for TLR9 and IL-12 showed higher fungal loads and rates of mortality compared to control mice after 30 days of infection. The association between CPG and rPb27 induced a high level of protection against Paracoccidioidomycosis after the first 30 days of infection but not at 60 days. Our findings demonstrate that TLR 9 plays a role in the protection induced by immunization with rPb27 and confirms the importance of TLR9 in the initial protection against Paracoccidioidomycosis.

TLR9

Paracoccidioides

10.1016/j.micinf.2015.10.005

Cite

Citations (17)

Disruption of the inositol phosphorylceramide synthase gene affects Trypanosoma cruzi differentiation and infection capacity

PLoS neglected tropical diseases (2023)

Nailma Silva Aprigio dos Santos Carlos F. Estevez-Castro Juan P. Macêdo Daniela Ferreira Chame Thiago Castro‐Gomes

Sphingolipids (SLs) are essential components of all eukaryotic cellular membranes. In fungi, plants and many protozoa, the primary SL is inositol-phosphorylceramide (IPC). Trypanosoma cruzi is a protozoan parasite that causes Chagas disease (CD), a chronic illness for which no vaccines or effective treatments are available. IPC synthase (IPCS) has been considered an ideal target enzyme for drug development because phosphoinositol-containing SL is absent in mammalian cells and the enzyme activity has been described in all parasite forms of T . cruzi . Furthermore, IPCS is an integral membrane protein conserved amongst other kinetoplastids, including Leishmania major , for which specific inhibitors have been identified. Using a CRISPR-Cas9 protocol, we generated T . cruzi knockout (KO) mutants in which both alleles of the IPCS gene were disrupted. We demonstrated that the lack of IPCS activity does not affect epimastigote proliferation or its susceptibility to compounds that have been identified as inhibitors of the L . major IPCS. However, disruption of the T . cruzi IPCS gene negatively affected epimastigote differentiation into metacyclic trypomastigotes as well as proliferation of intracellular amastigotes and differentiation of amastigotes into tissue culture-derived trypomastigotes. In accordance with previous studies suggesting that IPC is a membrane component essential for parasite survival in the mammalian host, we showed that T . cruzi IPCS null mutants are unable to establish an infection in vivo , even in immune deficient mice.

Amastigote

Chagas Disease

Kinetoplastida

Gene knockout

10.1371/journal.pntd.0011646

Cite

Citations (3)