In Vitro Cellular Division of Trypanosoma abeli Reveals Two Pathways for Organelle Replication.

Since the observation of the great pleomorphism of fish trypanosomes, in vitro culture has become an important tool to support taxonomic studies investigating the biology of cultured parasites, such as their structure, growth dynamics, and cellular cycle. Relative to their biology, ex vivo and in vitro studies have shown that these parasites, during the multiplication process, duplicate and segregate the kinetoplast before nucleus replication and division. However, the inverse sequence (the nucleus divides before the kinetoplast) has only been documented for a species of marine fish trypanosomes on a single occasion. Now, this previously rare event was observed in Trypanosoma abeli, a freshwater fish trypanosome. Specifically, from 376 cultured parasites in the multiplication process, we determined the sequence of organelle division for 111 forms; 39% exhibited nucleus duplication prior to kinetoplast replication. Thus, our results suggest that nucleus division before the kinetoplast may not represent an accidental or erroneous event occurring in the main pathway of parasite reproduction, but instead could be a species-specific process of cell biology in trypanosomes, such as previously noticed for Leishmania. This "alternative" pathway for organelle replication is a new field to be explored concerning the biology of marine and freshwater fish trypanosomes.

In vitro cellular division of trypanosoma abeli reveals two pathways for organelle replication

Since the observation of the great pleomorphism of fish trypanosomes, in vitroculture has become an important tool to support taxonomic studies investigat-ing the biology of cultured parasites, such as their structure, growth dynamics,and cellular cycle. Relative to their biology, ex vivo and in vitro studies haveshown that these parasites, during the multiplication process, duplicate andsegregate the kinetoplast before nucleus replication and division. However,the inverse sequence (the nucleus divides before the kinetoplast) has onlybeen documented for a species of marine fish trypanosomes on a single occa-sion. Now, this previously rare event was observed inTrypanosoma abeli,afreshwater fish trypanosome. Specifically, from 376 cultured parasites in themultiplication process, we determined the sequence of organelle division for111 forms; 39% exhibited nucleus duplication prior to kinetoplast replication.Thus, our results suggest that nucleus division before the kinetoplast may notrepresent an accidental or erroneous event occurring in the main pathway ofparasite reproduction, but instead could be a species-specific process of cellbiology in trypanosomes, such as previously noticed forLeishmania. This "al-ternative" pathway for organelle replication is a new field to be explored con-cerning the biology of marine and freshwater fish trypanosomes.

In vitro cellular division of trypanosoma abeli reveals two pathways for organelle replication

Since the observation of the great pleomorphism of fish trypanosomes, in vitroculture has become an important tool to support taxonomic studies investigat-ing the biology of cultured parasites, such as their structure, growth dynamics,and cellular cycle. Relative to their biology, ex vivo and in vitro studies haveshown that these parasites, during the multiplication process, duplicate andsegregate the kinetoplast before nucleus replication and division. However,the inverse sequence (the nucleus divides before the kinetoplast) has onlybeen documented for a species of marine fish trypanosomes on a single occa-sion. Now, this previously rare event was observed inTrypanosoma abeli,afreshwater fish trypanosome. Specifically, from 376 cultured parasites in themultiplication process, we determined the sequence of organelle division for111 forms; 39% exhibited nucleus duplication prior to kinetoplast replication.Thus, our results suggest that nucleus division before the kinetoplast may notrepresent an accidental or erroneous event occurring in the main pathway ofparasite reproduction, but instead could be a species-specific process of cellbiology in trypanosomes, such as previously noticed forLeishmania. This "al-ternative" pathway for organelle replication is a new field to be explored con-cerning the biology of marine and freshwater fish trypanosomes.

Corrigendum: Lipid Bodies as Sites of Prostaglandin E2 Synthesis During Chagas Disease: Impact in the Parasite Escape Mechanism.

[This corrects the article on p. 499 in vol. 9, PMID: 29616011.].

Lipid Bodies as Sites of Prostaglandin E2 Synthesis During Chagas Disease: Impact in the Parasite Escape Mechanism.

During Chagas disease, the Trypanosoma cruzi can induce some changes in the host cells in order to escape or manipulate the host immune response. The modulation of the lipid metabolism in the host phagocytes or in the parasite itself is one feature that has been observed. The goal of this mini review is to discuss the mechanisms that regulate intracellular lipid body (LB) biogenesis in the course of this parasite infection and their meaning to the pathophysiology of the disease. The interaction host-parasite induces LB (or lipid droplet) formation in a Toll-like receptor 2-dependent mechanism in macrophages and is enhanced by apoptotic cell uptake. Simultaneously, there is a lipid accumulation in the parasite due to the incorporation of host fatty acids. The increase in the LB accumulation during infection is correlated with an increase in the synthesis of PGE2 within the host cells and the parasite LBs. Moreover, the treatment with fatty acid synthase inhibitor C75 or non-steroidal anti-inflammatory drugs such as NS-398 and aspirin inhibited the LB biogenesis and also induced the down modulation of the eicosanoid production and the parasite replication. These findings show that LBs are organelles up modulated during the course of infection. Furthermore, the biogenesis of the LB is involved in the lipid mediator generation by both the macrophages and the parasite triggering escape mechanisms.

Lipid Body Organelles within the Parasite Trypanosoma cruzi: A Role for Intracellular Arachidonic Acid Metabolism.

Most eukaryotic cells contain varying amounts of cytosolic lipidic inclusions termed lipid bodies (LBs) or lipid droplets (LDs). In mammalian cells, such as macrophages, these lipid-rich organelles are formed in response to host-pathogen interaction during infectious diseases and are sites for biosynthesis of arachidonic acid (AA)-derived inflammatory mediators (eicosanoids). Less clear are the functions of LBs in pathogenic lower eukaryotes. In this study, we demonstrated that LBs, visualized by light microscopy with different probes and transmission electron microscopy (TEM), are produced in trypomastigote forms of the parasite Trypanosoma cruzi, the causal agent of Chagas' disease, after both host interaction and exogenous AA stimulation. Quantitative TEM revealed that LBs from amastigotes, the intracellular forms of the parasite, growing in vivo have increased size and electron-density compared to LBs from amastigotes living in vitro. AA-stimulated trypomastigotes released high amounts of prostaglandin E2 (PGE2) and showed PGE2 synthase expression. Raman spectroscopy demonstrated increased unsaturated lipid content and AA incorporation in stimulated parasites. Moreover, both Raman and MALDI mass spectroscopy revealed increased AA content in LBs purified from AA-stimulated parasites compared to LBs from unstimulated group. By using a specific technique for eicosanoid detection, we immunolocalized PGE2 within LBs from AA-stimulated trypomastigotes. Altogether, our findings demonstrate that LBs from the parasite Trypanosoma cruzi are not just lipid storage inclusions but dynamic organelles, able to respond to host interaction and inflammatory events and involved in the AA metabolism. Acting as sources of PGE2, a potent immunomodulatory lipid mediator that inhibits many aspects of innate and adaptive immunity, newly-formed parasite LBs may be implicated with the pathogen survival in its host.

Host Lipid Bodies as Platforms for Intracellular Survival of Protozoan Parasites.

Pathogens induce several changes in the host cell signaling and trafficking mechanisms in order to evade and manipulate the immune response. One prominent pathogen-mediated change is the formation of lipid-rich organelles, termed lipid bodies (LBs) or lipid droplets, in the host cell cytoplasm. Protozoan parasites, which contribute expressively to the burden of infectious diseases worldwide, are able to induce LB genesis in non-immune and immune cells, mainly macrophages, key players in the initial resistance to the infection. Under host-parasite interaction, LBs not only accumulate in the host cytoplasm but also relocate around and move into parasitophorous vacuoles. There is increasing evidence that protozoan parasites may target host-derived LBs either for gaining nutrients or for escaping the host immune response. Newly formed, parasite-induced LBs may serve as lipid sources for parasite growth and also produce inflammatory mediators that potentially act in the host immune response deactivation. In this mini review, we summarize current knowledge on the formation and role of host LBs as sites exploited by intracellular protozoan parasites as a strategy to maintain their own survival.

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

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.