Chloroquine inhibits Paracoccidioides brasiliensis survival within human monocytes by limiting the availability of intracellular iron

Microbiology and Immunology
Luciane Alarcão Dias-MelicioAngela Maria Victoriano de Campos Soares

Abstract

The mechanisms used by Paracoccidioides brasiliensis(Pb 18) to survive into monocytes are not clear. Cellular iron metabolism is of critical importance to the growth of several intracellular pathogens, including P. brasiliensis, whose capacity to multiply in mononuclear phagocytes is dependent on the availability of intracellular iron. Chloroquine, by virtue of its basic properties, has been shown to prevent release of iron from holotransferrin by raising endocytic and lysosomal pH, and thereby interfering with normal iron metabolism. Then, in view of this, we have studied the effects of CHLOR on P. brasiliensis multiplication in human monocytes and its effect on the murine paracoccidioidomycosis. CHLOR induced human monocytes to kill P. brasiliensis. The effect of CHLOR was reversed by FeNTA, an iron compound that is soluble at neutral to alkaline pH, but not by holotransferrin, which releases iron only in an acidic environment. CHLOR treatment of Pb 18-infected BALB/c mice significantly reduced the viable fungi recovery from lungs, during three different periods of evaluation, in a dose-dependent manner. This study demonstrates that iron is of critical importance to the survival of P. brasiliensis yeasts within human monocyte...Continue Reading

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Citations

May 17, 2014·PLoS Neglected Tropical Diseases·Elisa Flávia Luiz Cardoso BailãoCélia Maria de Almeida Soares
Nov 19, 2010·Critical Reviews in Immunology·Adam W Mailloux, M Rita I Young
Oct 29, 2008·Current Opinion in Microbiology·Nicole M Cooney, Bruce S Klein
Jul 17, 2007·International Journal of Antimicrobial Agents·Jean-Marc RolainDidier Raoult
May 26, 2012·Yeast·Guilherme Augusto BiondoAngela Maria Victoriano de Campos Soares
May 4, 2016·Veterinary Microbiology·Leticia T GresslerAgueda Castagna de Vargas
Jul 3, 2013·Trends in Microbiology·James W KronstadWon Hee Jung
Jul 24, 2012·Microbes and Infection·Ana Paula Bordon-GracianiAngela Maria Victoriano de Campos Soares
Apr 26, 2007·FEMS Immunology and Medical Microbiology·Luciane Alarcão Dias-MelicioAngela Maria Victoriano Campos Soares
Aug 30, 2018·PloS One·Tatiane Fernanda SylvestreRinaldo Poncio Mendes
Jan 7, 2021·Journal of Fungi·Aparecido Ferreira de SouzaCélia Maria de Almeida Soares
Nov 13, 2020·Frontiers in Cellular and Infection Microbiology·Qian Shen, Chad A Rappleye

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