Modulation of host cell mechanics by <i>Trypanosoma cruzi</i>

Mott, G. Adam; Lenormand, Guillaume; Costales, Jaime A.; Fredberg, Jeffrey J.; Burleigh, Barbara A.

doi:10.1002/jcp.21606

Cited by 39 publications

(36 citation statements)

References 50 publications

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“…cruzi invasion leads to disruption of the host cell cytoskeleton, intracellular trafficking, and tissue architecture. The cytoskeleton of the host cell has been shown to play an important role during pathogen invasion, establishment, and replication in the cytoplasm (43). We identified a number of genes associated with the host cell cytoskeleton and intracellular trafficking that were differentially expressed primarily during the late phase of the T. cruzi infection of murine cardiomyocytes (Fig.…”

Section: Resultsmentioning

confidence: 99%

Trypanosoma cruzi Infection Induces a Global Host Cell Response in Cardiomyocytes

et al. 2011

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Chagas' disease, caused by the hemoflagellate protozoan Trypanosoma cruzi, affects millions of people in South and Central America. Chronic chagasic cardiomyopathy, the most devastating manifestation of this disease, occurs in approximately one-third of infected individuals. Events associated with the parasite's tropism for and invasion of cardiomyocytes have been the focus of intense investigation in recent years. In the present study, we use murine microarrays to investigate the cellular response caused by invasion of primary murine cardiomyocytes by T. cruzi trypomastigotes. These studies identified 353 murine genes that were differentially expressed during the early stages of invasion and infection of these cells. Genes associated with the immune response, inflammation, cytoskeleton organization, cell-cell and cell-matrix interactions, apoptosis, cell cycle, and oxidative stress are among those affected during the infection. Our data indicate that T. cruzi induces broad modulations of the host cell machinery in ways that provide insight into how the parasite survives, replicates, and persists in the infected host and ultimately defines the clinical outcome of the infection.

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Section: Resultsmentioning

confidence: 99%

Trypanosoma cruzi Infection Induces a Global Host Cell Response in Cardiomyocytes

et al. 2011

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“…The role of L. donovani-specific amastin in parasite survival and sustainment of infection has recently been reported (30). Parasite-induced changes in the host macrophage cytoskeleton and its associated components have also been suggested to contribute to the altered immune status that supports parasite sustainment (41)(42)(43). However, the detailed molecular mechanism underlying such a host-pathogen relationship remains unresolved.…”

Section: Discussionmentioning

confidence: 99%

Wnt5a Signaling Promotes Host Defense against Leishmania donovani Infection

Chakraborty

Kurati

Mahata

et al. 2017

The Journal of Immunology

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Leishmania donovani infects macrophages, disrupting immune homeostasis. The underlying mechanism that sustains infection remains unresolved. In view of the potential of Wnt5a signaling to support immune homeostasis, we evaluated the interrelationship of Wnt5a signaling and Leishmania donovani infection. Upon infecting macrophages separately with antimony drug–sensitive and –resistant L. donovani, we noted disruption in the steady-state level of Wnt5a. Moreover, inhibition of Wnt5a signaling by small interfering RNA transfection in vitro or by use of inhibitor of Wnt production in vivo led to an increase in cellular parasite load. In contrast, treatment of macrophages with recombinant Wnt5a caused a decrease in the load of antimony-sensitive and -resistant parasites, thus confirming that Wnt5a signaling antagonizes L. donovani infection. Using inhibitors of the Wnt5a signaling intermediates Rac1 and Rho kinase, we demonstrated that Wnt5a-mediated inhibition of parasite infection in macrophages is Rac1/Rho dependent. Furthermore, phalloidin staining and reactive oxygen species estimation of Wnt5a-treated macrophages suggested that a Wnt5a-Rac/Rho–mediated decrease in parasite load is associated with an increase in F- actin assembly and NADPH oxidase activity. Moreover, live microscopy of L. donovani–infected macrophages treated with Wnt5a demonstrated increased endosomal/lysosomal fusions with parasite-containing vacuoles (parasitophorous vacuoles [PV]). An increase in PV–endosomal/lysosomal fusion accompanied by augmented PV degradation in Wnt5a-treated macrophages was also apparent from transmission electron microscopy of infected cells. Our results suggest that, although L. donovani evades host immune response, at least in part through inhibition of Wnt5a signaling, revamping Wnt5a signaling can inhibit L. donovani infection, irrespective of drug sensitivity or resistance.

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“…At 8-16 h after the cellular invasion by trypomastigote forms of T. cruzi, the parasites egress the vacuole and differentiate into the amastigote form in the cytoplasm, where they begin to divide (41). Because our data demonstrate that the caspase-1 signaling induced by T. cruzi occurs at a later stage (24 h postinfection) compared with the caspase-1 activation triggered by other pathogens, we speculate that the parasites need to escape of the phagosome to trigger the inflammasome.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis-Associated Speck–like Protein Containing a Caspase Recruitment Domain Inflammasomes Mediate IL-1β Response and Host Resistance to Trypanosoma cruzi Infection

Silva

Sesti-Costa

Silveira

et al. 2013

The Journal of Immunology

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The innate immune response to Trypanosoma cruzi infection comprises several pattern recognition receptors (PRRs), including TLR-2, -4, -7, and -9, as well as the cytosolic receptor Nod1. However, there are additional PRRs that account for the host immune responses to T. cruzi. In this context, the nucleotide-binding oligomerization domain–like receptors (NLRs) that activate the inflammasomes are candidate receptors that deserve renewed investigation. Following pathogen infection, NLRs form large molecular platforms, termed inflammasomes, which activate caspase-1 and induce the production of active IL-1β and IL-18. In this study, we evaluated the involvement of inflammasomes in T. cruzi infection and demonstrated that apoptosis-associated speck–like protein containing a caspase recruitment domain (ASC) inflammasomes, including NLR family, pyrin domain–containing 3 (NLRP3), but not NLR family, caspase recruitment domain–containing 4 or NLR family, pyrin domain–containing 6, are required for triggering the activation of caspase-1 and the secretion of IL-1β. The mechanism by which T. cruzi mediates the activation of the ASC/NLRP3 pathway involves K+ efflux, lysosomal acidification, reactive oxygen species generation, and lysosomal damage. We also demonstrate that despite normal IFN-γ production in the heart, ASC−/− and caspase-1−/− infected mice exhibit a higher incidence of mortality, cardiac parasitism, and heart inflammation. These data suggest that ASC inflammasomes are critical determinants of host resistance to infection with T. cruzi.

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Modulation of host cell mechanics by Trypanosoma cruzi

Cited by 39 publications

References 50 publications

Trypanosoma cruzi Infection Induces a Global Host Cell Response in Cardiomyocytes

Trypanosoma cruzi Infection Induces a Global Host Cell Response in Cardiomyocytes

Wnt5a Signaling Promotes Host Defense against Leishmania donovani Infection

Apoptosis-Associated Speck–like Protein Containing a Caspase Recruitment Domain Inflammasomes Mediate IL-1β Response and Host Resistance to Trypanosoma cruzi Infection

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