Lipid bodies: Structural markers of inflammatory macrophages in innate immunity.

OBJECTIVE AND DESIGN: The correlation between innate immune responses and formation of cytoplasmic lipid bodies (LBs) was investigated in vivo in inflammatory macrophages from rats infected with Trypanosoma cruzi, the intracellular parasite which causes Chagas' disease. MATERIAL AND METHODS: We used an experimental model of high-dose irradiation prior to infection, which depletes the humoral and cellular immune responses except for the phagocytic activity of macrophages. Rats, irradiated or not, were infected with T. cruzi and macrophages from different origins (peritoneum, heart, uterus) were studied by transmission electron microscopy (TEM). RESULTS: As documented by quantitative TEM, innate immune responses induced prominent formation, structural changes and intracellular interactions of LBs. LBs significantly increased their size and changed their osmiophilia in response to both infection alone and when macrophages were challenged with irradiation-induced increased parasite load. Remarkably, a consistent LB-phagolysosome association was identified. LBs were surrounding, attached to or internalized by phagolysosomes. CONCLUSIONS: We demonstrated that LBs are dynamic organelles notably involved in the host response to acute T. cruzi infection, an event that may be important for pathogen control during innate immunity. Our findings highlight LBs as structural markers of the innate immune responses in phagocytic cells.

Macrophage lipid body induction by Chagas disease in vivo: putative intracellular domains for eicosanoid formation during infection.

Lipid bodies (LB), lipid-rich inclusions abundantly present in cells engaged in inflammation, are specialized intracellular domains involved in generating inflammatory mediators, the eicosanoids. Since the acute Trypanosoma cruzi infection triggers a potent inflammatory reaction characterized by a great increase of peripheral blood monocyte (PBM) and macrophage numbers, we investigated the LB occurrence in these cells. The experimental rat infection by T. cruzi (Y strain) induced significant increase of the LB numbers in peritoneal macrophages at day 6 and 12, accompanied by significant enhancement of Prostaglandin E(2) (PGE(2)) production, as measured by EIA. At day 12, ultrastructural analysis of the heart, a target organ of the disease, showed numerous macrophages with LB prominently increased in number (mean of 8.3 per section view, range of 1-25) compared to controls (mean of 2.6 per section view, range of 0-3) and size. PBM from all groups rarely showed LB. Our results demonstrate, for the first time, that T. cruzi infection in rats elicits important LB formation in inflammatory macrophages but not in PBM. The increase in LB numbers during infection positively correlates with increased generation of PGE(2), suggesting that LB may have a role in the heightened eicosanoid production observed during T. cruzi infection.