Abstract
Lipids from microorganisms are ligands of Toll like receptors (TLRs) and modulate the innate immune response. Herein, we analyze in vitro the effect of total lipid extracts from Trypanosoma cruzi amastigotes of RA and K98 strains (with polar biological behavior) on the induction of the inflammatory response and the involvement of TLRs in this process. We demonstrated that total lipid extracts from both strains induced lipid body formation, cyclooxygenase-2 expression and TNF-α and nitric oxide release in macrophages, as well as NF-κB activation and IL-8 release in HEK cells specifically through a TLR2/6 dependent pathway. We also evaluated the inflammatory response induced by total lipid extracts obtained from lysed parasites that were overnight incubated to allow the action of parasite hydrolytic enzymes, such as Phospholipase A1, over endogenous phospholipids. After incubation, these total lipid extracts showed a significantly reduced pro-inflammatory response, which could be attributed to the changes in the content of known bioactive lipid molecules like lysophospholipids and fatty acids, here reported. Moreover, analyses of total fatty acids in each lipid extract were performed by gas chromatography-mass spectrometry. Our results indicate a relevant role of T. cruzi lipids in the induction of a pro-inflammatory response through the TLR2/6 pathway that could contribute to the modulation of the immune response and host survival.
Highlights
Trypanosoma cruzi is the etiological agent of Chagas disease that represents a public health problem in Latin America with a recent spreading to non-endemic areas due to human migration; it is currently estimated that nearly 7 million people are infected by this protozoan parasite (WHO Chagas disease (American trypanosomiasis), 2017)1
We analyzed by thin layer chromatography (TLC) the total lipid extract from T. cruzi amastigotes of the low virulence strain K98 (K98) as well as that corresponding to incubated parasites (K98inc)
The comparison between RAinc vs RA and K98inc vs. K98 displayed a reduction in this cytokine level of ∼8.91 and 11.33 folds, respectively. This is a novel report that describes the biological effect of total lipid extracts from amastigotes of two T. cruzi strains, which belong to different Discrete Typing Units (DTUs) and possess polar biological behavior: RA (Tc VI, high virulence) and K98 (Tc I, low virulence) (González Cappa et al, 1980, 1981; Zingales et al, 2009)
Summary
Trypanosoma cruzi is the etiological agent of Chagas disease that represents a public health problem in Latin America with a recent spreading to non-endemic areas due to human migration; it is currently estimated that nearly 7 million people are infected by this protozoan parasite (WHO Chagas disease (American trypanosomiasis), 2017). Amastigote Lipids Generate Pro-inflammatory Response of genetics as well as biological behavior and great efforts have been made to identify molecules involved in parasite–host cell interaction, which may contribute to the pathogenesis of Chagas disease (Zingales et al, 2009). The first evidences related to phospholipid degrading enzymes in T. cruzi were associated to the inflammatory responses that appear surrounding degenerating amastigote nests in various tissues of Chagas disease patients, suggesting that the inflammation observed might be attributed to phospholipid breakdown products such as free fatty acids (FFA) and lysophospholipids (Belaunzarán et al, 2011). We have already demonstrated in all stages of T. cruzi RA strain a rapid and extensive breakdown of endogenous phospholipids upon parasite death, with a concomitant accumulation of FFA, that could be attributed to T. cruzi Phospholipase A1 (Wainszelbaum et al, 2001)
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