Inhibition of autolysosome formation in host autophagy by Trypanosoma cruzi infection

Onizuka, Yoko; Takahashi, Chiyuki; Uematsu, Ami; Shinjo, Shoko; Seto, Eri; Nakajima‐Shimada, Junko

doi:10.1016/j.actatropica.2017.02.021

Cited by 24 publications

(22 citation statements)

References 24 publications

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“…The role of NLRP3 in the autolysosomes formation could be considered a host response against the manipulation of autophagic machinery by T. cruzi, since in a fibrosarcoma cell line, in which NLRP3 seems not be activated, T. cruzi inhibits the autolysosome formation. 71 Although it remains to be elucidated how NLRP3 induces autolysosomes formation, our data brings some new pieces to this complex puzzle of cross-talks between inflammasomes and autophagy during infections by describing autophagy as an autonomous cellular mechanism mediated by NLRP3 to control T. cruzi infection.…”

Section: Pharmacologic Inhibition Of Autophagy Renders Macrophages Frommentioning

confidence: 84%

Frontline Science: Autophagy is a cell autonomous effector mechanism mediated by NLRP3 to control Trypanosoma cruzi infection

Matteucci

Pereira

Weinlich

et al. 2019

Journal of Leukocyte Biology

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Autophagy and inflammasome activation are cell‐autonomous and cross‐regulated processes involved in host resistance against infections. Our group previously described that NLRP3 inflammasome is required for the control of Trypanosoma cruzi, the causative agent of Chagas disease. However, the involvement of autophagy in this process was unclear. Here, we demonstrated that T. cruzi was able to induce an increase in LC3‐II expression as well as autophagosome and autolysosome formation in peritoneal macrophages (PMs) from C57BL/6 wild‐type mice. Moreover, the pharmacologic inhibition of autophagic machinery impaired the ability of PMs to control T. cruzi replication. Importantly, NLRP3 was required for the induction of a regular autophagic flux in response to T. cruzi, an effect mediated by its participation in the autolysosomes formation. Together, these results indicate autophagy as an effector mechanism mediated by NLRP3 to control T. cruzi infection.

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Section: Pharmacologic Inhibition Of Autophagy Renders Macrophages Frommentioning

confidence: 84%

Frontline Science: Autophagy is a cell autonomous effector mechanism mediated by NLRP3 to control Trypanosoma cruzi infection

Matteucci

Pereira

Weinlich

et al. 2019

Journal of Leukocyte Biology

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“…Host autophagy machinery is crucial for cellular pathways in immune responses, including lymphocyte activation and intracellular parasite infections, as previously demonstrated [16]. In the case of in vitro T. cruzi infection, some reports described the association of pathogen control with host autophagy and mTORC1 pathway [18,26,28,29], even with some conflicting results. In this work, we evaluated the upregulation of autophagy in T. cruzi infection in vivo and autophagy upmodulation/ mTORC1 inhibition by rapamycin as a mechanism of controlling inflammation and cardiac damage triggered by the parasite.…”

Section: Discussionmentioning

confidence: 95%

“…First, we evaluated if autophagy in cardiac fibers is upregulated in vivo after T. cruzi infection, as observed in the liver [17,25], and in vitro in different lineage cells by others [26,28,29]. To this end, the mice were infected and the presence of LC3 puncta was investigated by immunostaining in cardiac ventricles sections ( Fig.…”

Section: Autophagy Is Upregulated During Chagasic Cardiomyopathy In Vivomentioning

confidence: 99%

Rapamycin Treatment Reduces Acute Myocarditis Induced by <b><i>Trypanosoma cruzi</i></b> Infection

et al. 2019

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Chagas disease affects millions of people mainly in Latin America and is a protozoan illness caused by the parasite Trypanosoma cruzi. Chagasic cardiomyopathy is the leading cause of mortality of infected patients, due to compromised electrical and mechanical cardiac function induced by tissue remodeling, especially fibrosis, and lymphocytic infiltration. Some cellular biochemical pathways can be protective to the heart, and we tested if the in vivo activation of the autophagic machinery by rapamycin could reduce parasite-induced myocarditis. Regarding the expression of LC3, an autophagy marker, we observed its upregulation in the cardiac tissue of infected untreated mice. However, after rapamycin treatment, an autophagy inducer, infected mice showed reduced electrical cardiac dysfunctions, myocarditis, cardiac damage, and reduced production of pro-inflammatory cytokines by the heart. On the other hand, the parasite's life cycle was not affected, and we observed no modulations in cardiac tissue or blood parasitemia. Our data indicate that, at least partially, autophagy induction controls inflammation in the heart¸ illustrating the complexity of the pathways that concur to the development of the infection.

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“…A recent work showed that autophagosome formation was induced by T. cruzi infection. By quantifying the number of LC3 puncta in cells infected with T. cruzi, the authors demonstrated a gradual increment of these vesicles, which reach a maximum level at 9 h post infection [74]. Unpublished data from our laboratory show that the percentage of cells with more than five LC3-positive vesicles/cell was significantly increased in cells infected with TCT of T. cruzi Y strain, compared to control (Figure 2).…”

Section: Invasion Of Trypomastigotesmentioning

confidence: 86%

“…Onisuka and colleagues [74] also showed that T. cruzi infection inhibited the normal maturation of autophagosomes to autolysosomes (autophagic flux). Our investigation concerning this point was not conclusive.…”

Section: Invasion Of Trypomastigotesmentioning

confidence: 98%

Autophagy: A necessary process during the Trypanosoma cruzi life-cycle

Salassa

Romano

2018

Virulence

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Autophagy is a well-conserved process of self-digestion of intracellular components. T. cruzi is a protozoan parasite with a complex life-cycle that involves insect vectors and mammalian hosts. Like other eukaryotic organisms, T. cruzi possesses an autophagic pathway that is activated during metacyclogenesis, the process that generates the infective forms of parasites. In addition, it has been demonstrated that mammalian autophagy has a role during host cell invasion by T. cruzi, and that T. cruzi can modulate this process to its own benefit. This review describes the latest findings concerning the participation of autophagy in both the T. cruzi differentiation processes and during the interaction of parasites within the host cells. Data to date suggest parasite autophagy is important for parasite survival and differentiation, which offers interesting prospects for therapeutic strategies. Additionally, the interruption of mammalian autophagy reduces the parasite infectivity, interfering with the intracellular cycle of T. cruzi inside the host. However, the impact on other stages of development, such as the intracellular replication of parasites is still not clearly understood. Further studies in this matter are necessaries to define the integral effect of autophagy on T. cruzi infection with both in vitro and in vivo approaches.

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Inhibition of autolysosome formation in host autophagy by Trypanosoma cruzi infection

Cited by 24 publications

References 24 publications

Frontline Science: Autophagy is a cell autonomous effector mechanism mediated by NLRP3 to control Trypanosoma cruzi infection

Frontline Science: Autophagy is a cell autonomous effector mechanism mediated by NLRP3 to control Trypanosoma cruzi infection

Rapamycin Treatment Reduces Acute Myocarditis Induced by <b><i>Trypanosoma cruzi</i></b> Infection

Autophagy: A necessary process during the Trypanosoma cruzi life-cycle

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