Abstract
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.
Highlights
Chagas disease represents an infectious condition classified by the World Health Organization (WHO) as a neglected illness
Based on the effects that T. cruzi infection and apoptotic cell uptake cause on lipid body (LB) formation in the host cell, it has been investigated whether modulation of the formation of this organelle could impact the replication of the parasite (D’Avila et al, 2011). It was tested the effect of two nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin (COX-1 and COX-2 inhibitor) and NS- 398 (COX-2 inhibitor) which, in addition to their COX inhibitory effect, inhibit COXindependent LB formation (Bozza et al, 1996, 2002). Both aspirin and NS-398 inhibited the LB biogenesis in infected macrophages in the presence or absence of apoptotic cells, suppressing the T. cruzi effects on LB-derived PGE2 synthesis, and reversing the enhancement on parasite replication induced by apoptotic cells (Figure 2)
Formed host LBs are distinguished for their efficiency to synthesize lipid inflammatory mediators, such as PGE2 and to compartmentalize eicosanoid-forming enzymes, such as COX-2 (Yu et al, 1998; Bozza et al, 2002; D’Avila et al, 2006, 2011)
Summary
Chagas disease represents an infectious condition classified by the World Health Organization (WHO) as a neglected illness. A distinguishing aspect of Chagas disease-triggered macrophages is the increased numbers of distinct cytoplasmic organelles called lipid bodies (LBs) (Figure 1) (Melo et al, 2003; D’Avila et al, 2011).
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