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Lipid bodies: inflammatory organelles implicated in host-Trypanosoma cruzi interplay during innate immune responses.

D'Avila H, Toledo DA, Melo RC - Mediators Inflamm. (2012)

Bottom Line: A distinguishing feature of Chagas' disease-triggered macrophages is the presence of increased numbers of distinct cytoplasmic organelles termed lipid bodies or lipid droplets.These organelles are actively formed in response to the parasite and are sites for synthesis and storage of inflammatory mediators.The increased knowledge of lipid bodies in pathogenic mechanisms of infections may not only contribute to the understanding of pathogen-host interactions but may also identify new targets for intervention.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular Biology, Department of Biology, Federal University of Juiz de Fora (UF JF), 36036-900 Juiz de Fora, MG, Brazil.

ABSTRACT
The flagellated protozoa Trypanosoma cruzi is the causal agent of Chagas' disease, a significant public health issue and still a major cause of morbidity and mortality in Latin America. Acute Chagas' disease elicits a strong inflammatory response. In order to control the parasite multiplication, cells of the monocytic lineage are highly mobilized. Monocyte differentiation leads to the formation of phagocytosing macrophages, which are strongly activated and direct host defense. A distinguishing feature of Chagas' disease-triggered macrophages is the presence of increased numbers of distinct cytoplasmic organelles termed lipid bodies or lipid droplets. These organelles are actively formed in response to the parasite and are sites for synthesis and storage of inflammatory mediators. This review covers current knowledge on lipid bodies elicited by the acute Chagas' disease within inflammatory macrophages and discusses the role of these organelles in inflammation. The increased knowledge of lipid bodies in pathogenic mechanisms of infections may not only contribute to the understanding of pathogen-host interactions but may also identify new targets for intervention.

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Uptake of apoptotic cells by macrophages induces lipid body formation and PGE2 synthesis during Trypanosoma cruzi infection. LB formation (a) and prostaglandin E2 (PGE2) synthesis (b) by mice macrophages infected in vitro with T. cruzi alone or co-cultured with apoptotic cells for 24 hours. Each bar represents the mean ± standard error of the mean (SEM) from 50 consecutively counted macrophages from at least 4 independent pools of 3 animals each. Statistically significant (P # 0.05) differences between control and infected or stimulated groups are indicated by asterisks; Mϕ, macrophages. In (c), a large typical apoptotic body (outlined in red in (ci)) showing very condensed, electron-dense nuclear chromatin and degenerating mitochondria (red arrowheads) is seen within a heart macrophage of a rat with 12 days of infection. Note that the apoptotic body is surrounded by several lipid bodies with distinct electron densities. Rats were infected with the Y strain of T. cruzi and the myocardium processed for transmission electron microscopy at day 12 of the acute infection. Reprinted from [35] with permission. Scale bar, 1 μm.
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fig6: Uptake of apoptotic cells by macrophages induces lipid body formation and PGE2 synthesis during Trypanosoma cruzi infection. LB formation (a) and prostaglandin E2 (PGE2) synthesis (b) by mice macrophages infected in vitro with T. cruzi alone or co-cultured with apoptotic cells for 24 hours. Each bar represents the mean ± standard error of the mean (SEM) from 50 consecutively counted macrophages from at least 4 independent pools of 3 animals each. Statistically significant (P # 0.05) differences between control and infected or stimulated groups are indicated by asterisks; Mϕ, macrophages. In (c), a large typical apoptotic body (outlined in red in (ci)) showing very condensed, electron-dense nuclear chromatin and degenerating mitochondria (red arrowheads) is seen within a heart macrophage of a rat with 12 days of infection. Note that the apoptotic body is surrounded by several lipid bodies with distinct electron densities. Rats were infected with the Y strain of T. cruzi and the myocardium processed for transmission electron microscopy at day 12 of the acute infection. Reprinted from [35] with permission. Scale bar, 1 μm.

Mentions: Uptake of apoptotic bodies, a process termed efferocytosis, is able to impact on host inflammatory mediator production and susceptibility to infection [44, 60, 61]. It was recently demonstrated that efferocytosis may affect lipid body formation and PGE2 synthesis during the T. cruzi infection [35] (Figure 6). These authors showed that the uptake of apoptotic cells, but not living or necrotic cells by cultured macrophages, triggers lipid body formation in the absence of infection. However, when infected macrophages are exposed to apoptotic cells, the efferocytosis process amplifies the effects of the parasite on lipid body formation leading to a higher lipid body accumulation compared to noninfected cells exposed to apoptotic bodies (Figure 6). Consistent with the lipid body function in inflammation, as discussed in Section 3, the uptake of apoptotic cells by both infected and noninfected macrophages induces increased lipid body-derived PGE2 synthesis. Interestingly, 24 h after the uptake of apoptotic cells by noninfected macrophages, newly formed lipid bodies show in situ both COX-2 and PGE2, similarly to infected cells [35].


Lipid bodies: inflammatory organelles implicated in host-Trypanosoma cruzi interplay during innate immune responses.

D'Avila H, Toledo DA, Melo RC - Mediators Inflamm. (2012)

Uptake of apoptotic cells by macrophages induces lipid body formation and PGE2 synthesis during Trypanosoma cruzi infection. LB formation (a) and prostaglandin E2 (PGE2) synthesis (b) by mice macrophages infected in vitro with T. cruzi alone or co-cultured with apoptotic cells for 24 hours. Each bar represents the mean ± standard error of the mean (SEM) from 50 consecutively counted macrophages from at least 4 independent pools of 3 animals each. Statistically significant (P # 0.05) differences between control and infected or stimulated groups are indicated by asterisks; Mϕ, macrophages. In (c), a large typical apoptotic body (outlined in red in (ci)) showing very condensed, electron-dense nuclear chromatin and degenerating mitochondria (red arrowheads) is seen within a heart macrophage of a rat with 12 days of infection. Note that the apoptotic body is surrounded by several lipid bodies with distinct electron densities. Rats were infected with the Y strain of T. cruzi and the myocardium processed for transmission electron microscopy at day 12 of the acute infection. Reprinted from [35] with permission. Scale bar, 1 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig6: Uptake of apoptotic cells by macrophages induces lipid body formation and PGE2 synthesis during Trypanosoma cruzi infection. LB formation (a) and prostaglandin E2 (PGE2) synthesis (b) by mice macrophages infected in vitro with T. cruzi alone or co-cultured with apoptotic cells for 24 hours. Each bar represents the mean ± standard error of the mean (SEM) from 50 consecutively counted macrophages from at least 4 independent pools of 3 animals each. Statistically significant (P # 0.05) differences between control and infected or stimulated groups are indicated by asterisks; Mϕ, macrophages. In (c), a large typical apoptotic body (outlined in red in (ci)) showing very condensed, electron-dense nuclear chromatin and degenerating mitochondria (red arrowheads) is seen within a heart macrophage of a rat with 12 days of infection. Note that the apoptotic body is surrounded by several lipid bodies with distinct electron densities. Rats were infected with the Y strain of T. cruzi and the myocardium processed for transmission electron microscopy at day 12 of the acute infection. Reprinted from [35] with permission. Scale bar, 1 μm.
Mentions: Uptake of apoptotic bodies, a process termed efferocytosis, is able to impact on host inflammatory mediator production and susceptibility to infection [44, 60, 61]. It was recently demonstrated that efferocytosis may affect lipid body formation and PGE2 synthesis during the T. cruzi infection [35] (Figure 6). These authors showed that the uptake of apoptotic cells, but not living or necrotic cells by cultured macrophages, triggers lipid body formation in the absence of infection. However, when infected macrophages are exposed to apoptotic cells, the efferocytosis process amplifies the effects of the parasite on lipid body formation leading to a higher lipid body accumulation compared to noninfected cells exposed to apoptotic bodies (Figure 6). Consistent with the lipid body function in inflammation, as discussed in Section 3, the uptake of apoptotic cells by both infected and noninfected macrophages induces increased lipid body-derived PGE2 synthesis. Interestingly, 24 h after the uptake of apoptotic cells by noninfected macrophages, newly formed lipid bodies show in situ both COX-2 and PGE2, similarly to infected cells [35].

Bottom Line: A distinguishing feature of Chagas' disease-triggered macrophages is the presence of increased numbers of distinct cytoplasmic organelles termed lipid bodies or lipid droplets.These organelles are actively formed in response to the parasite and are sites for synthesis and storage of inflammatory mediators.The increased knowledge of lipid bodies in pathogenic mechanisms of infections may not only contribute to the understanding of pathogen-host interactions but may also identify new targets for intervention.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular Biology, Department of Biology, Federal University of Juiz de Fora (UF JF), 36036-900 Juiz de Fora, MG, Brazil.

ABSTRACT
The flagellated protozoa Trypanosoma cruzi is the causal agent of Chagas' disease, a significant public health issue and still a major cause of morbidity and mortality in Latin America. Acute Chagas' disease elicits a strong inflammatory response. In order to control the parasite multiplication, cells of the monocytic lineage are highly mobilized. Monocyte differentiation leads to the formation of phagocytosing macrophages, which are strongly activated and direct host defense. A distinguishing feature of Chagas' disease-triggered macrophages is the presence of increased numbers of distinct cytoplasmic organelles termed lipid bodies or lipid droplets. These organelles are actively formed in response to the parasite and are sites for synthesis and storage of inflammatory mediators. This review covers current knowledge on lipid bodies elicited by the acute Chagas' disease within inflammatory macrophages and discusses the role of these organelles in inflammation. The increased knowledge of lipid bodies in pathogenic mechanisms of infections may not only contribute to the understanding of pathogen-host interactions but may also identify new targets for intervention.

Show MeSH
Related in: MedlinePlus