Paracoccidioides brasiliensis lipids modulate macrophage activity via Toll-dependent or independent mechanisms

FEMS Immunology and Medical Microbiology
Flávio V LouresVera L G Calich

Abstract

The macrophages are the first host cells that interact with the fungus Paracoccidioides brasiliensis, but the main mechanisms that regulate this interaction are not well understood. Because the role played by P. brasiliensis lipids in macrophage activation was not previously investigated, we aimed to assess the influence of diverse lipid fractions from P. brasiliensis yeasts in this process. The possible participation of TLR2 and TLR4 signaling was also evaluated using TLR2- and TLR4-defective macrophages. Four lipid-rich fractions were studied as follows: F1, composed by membrane phospholipids and neutral lipids, F2 by glycolipids of short chain, F3a by membrane glycoproteins anchored by glycosylphosphatidylinositol (GPI) groups, and F3b by glycolipids of long chain. All assayed lipid fractions were able to activate peritoneal macrophages and induce nitric oxide (NO) production. Importantly, the F1 and F3a fractions exerted opposite effects in the control of P. brasiliensis uptake and killing, but both fractions inhibited cytokines production. Furthermore, the increased NO production and expression of costimulatory molecules induced by F3a was shown to be TLR2 dependent although F1 used Toll-independent mechanisms. In conclusi...Continue Reading

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Citations

Oct 14, 2017·The Journal of Infectious Diseases·Lena F SchimkeAntonio Condino-Neto
Aug 22, 2018·Journal of Fungi·Laura Cristina García CarneroJosé Ascención Martínez Álvarez

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