Cryptic infections in mice with the Trypanosoma cruzi CL-14 clone

Sousa, Maria Auxiliadora de; Pereira, Solange

doi:10.1590/s0036-46651999000300014

Cited by 2 publications

(2 citation statements)

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“…cruzi cloned strains, CL Brener and CL-14, which were originally cloned from the parental CL strain [ 14 ]. In contrast to CL Brener, CL-14 is non-infectious and non-pathogenic in vivo , even when inoculated into newborn [ 15 , 16 ] or immune deficient, CD8 -/- mice [ 17 ] that are otherwise highly susceptible to T . cruzi infection.…”

Section: Introductionmentioning

confidence: 99%

Comparative transcriptome profiling of virulent and non-virulent Trypanosoma cruzi underlines the role of surface proteins during infection

et al. 2017

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Trypanosoma cruzi, the protozoan that causes Chagas disease, has a complex life cycle involving several morphologically and biochemically distinct stages that establish intricate interactions with various insect and mammalian hosts. It has also a heterogeneous population structure comprising strains with distinct properties such as virulence, sensitivity to drugs, antigenic profile and tissue tropism. We present a comparative transcriptome analysis of two cloned T. cruzi strains that display contrasting virulence phenotypes in animal models of infection: CL Brener is a virulent clone and CL-14 is a clone that is neither infective nor pathogenic in in vivo models of infection. Gene expression analysis of trypomastigotes and intracellular amastigotes harvested at 60 and 96 hours post-infection (hpi) of human fibroblasts revealed large differences that reflect the parasite’s adaptation to distinct environments during the infection of mammalian cells, including changes in energy sources, oxidative stress responses, cell cycle control and cell surface components. While extensive transcriptome remodeling was observed when trypomastigotes of both strains were compared to 60 hpi amastigotes, differences in gene expression were much less pronounced when 96 hpi amastigotes and trypomastigotes of CL Brener were compared. In contrast, the differentiation of the avirulent CL-14 from 96 hpi amastigotes to extracellular trypomastigotes was associated with considerable changes in gene expression, particularly in gene families encoding surface proteins such as trans-sialidases, mucins and the mucin associated surface proteins (MASPs). Thus, our comparative transcriptome analysis indicates that the avirulent phenotype of CL-14 may be due, at least in part, to a reduced or delayed expression of genes encoding surface proteins that are associated with the transition of amastigotes to trypomastigotes, an essential step in the establishment of the infection in the mammalian host. Confirming the role of members of the trans-sialidase family of surface proteins for parasite differentiation, transfected CL-14 constitutively expressing a trans-sialidase gene displayed faster kinetics of trypomastigote release in the supernatant of infected cells compared to wild type CL-14.

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Section: Introductionmentioning

confidence: 99%

Comparative transcriptome profiling of virulent and non-virulent Trypanosoma cruzi underlines the role of surface proteins during infection

et al. 2017

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“…Genome sequencing of the clone CL Brener, a TcVI strain, showed it is a hybrid strain containing two genotypes that belong to TcII and TcIII [ 4 ]. CL-14 is another clone derived from the CL strain that also belongs to the TcVI group, but in contrast to CL Brener, presents low virulence and is non-pathogenic, even when inoculated into newborn [ 5 – 7 ] or immune deficient, CD8 -/- mice [ 8 ]. Importantly, after inoculation in adult animals, CL-14 induces protective immunity and prevents the development of parasitemia and mortality following challenge with virulent T .…”

Section: Introductionmentioning

confidence: 99%

Gene expression network analyses during infection with virulent and avirulent Trypanosoma cruzi strains unveil a role for fibroblasts in neutrophil recruitment and activation

et al. 2020

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Chagas disease is caused by Trypanosoma cruzi , a protozoan parasite that has a heterogeneous population composed of a pool of strains with distinct characteristics, including variable levels of virulence. In previous work, transcriptome analyses of parasite genes after infection of human foreskin fibroblasts (HFF) with virulent (CL Brener) and non-virulent (CL-14) clones derived from the CL strain, revealed a reduced expression of genes encoding parasite surface proteins in CL-14 compared to CL Brener during the final steps of the intracellular differentiation from amastigotes to trypomastigotes. Here we analyzed changes in the expression of host genes during in vitro infection of HFF cells with the CL Brener and CL-14 strains by analyzing total RNA extracted from cells at 60 and 96 hours post-infection (hpi) with each strain, as well as from uninfected cells. Similar transcriptome profiles were observed at 60 hpi with both strains compared to uninfected samples. However, at 96 hpi, significant differences in the number and expression levels of several genes, particularly those involved with immune response and cytoskeleton organization, were observed. Further analyses confirmed the difference in the chemokine/cytokine signaling involved with the recruitment and activation of immune cells such as neutrophils upon T . cruzi infection. These findings suggest that infection with the virulent CL Brener strain induces a more robust inflammatory response when compared with the non-virulent CL-14 strain. Importantly, the RNA-Seq data also exposed an unexplored role of fibroblasts as sentinel cells that may act by recruiting neutrophils to the initial site of infection. This role for fibroblasts in the regulation of the inflammatory response during infection by T . cruzi was corroborated by measurements of levels of different chemokines/cytokines during in vitro infection and in plasma from Chagas disease patients as well as by neutrophil activation and migration assays.

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Cryptic infections in mice with the Trypanosoma cruzi CL-14 clone

Cited by 2 publications

References 2 publications

Comparative transcriptome profiling of virulent and non-virulent Trypanosoma cruzi underlines the role of surface proteins during infection

Comparative transcriptome profiling of virulent and non-virulent Trypanosoma cruzi underlines the role of surface proteins during infection

Gene expression network analyses during infection with virulent and avirulent Trypanosoma cruzi strains unveil a role for fibroblasts in neutrophil recruitment and activation

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