Photodynamic effects on Fonsecaea monophora conidia and RAW264.7 in vitro

Chromoblastomycosis (CBM), one of the neglected tropical diseases, is hard to cure and easy to be recurrent. Many studies suggest that macrophage is involved in the pathogenesis of chromoblastomycosis and the fungicidal effect of 5-Aminolaevulinic Acid-Based Photodynamic Therapy (ALA-PDT) against F. monophora (one of the main causative agent of chromoblastomycosis) has shown great promise. However, the fungicidal ability of ALA-PDT to F. monophora is still controversial and the molecular mechanism and immune mechanism of ALA-PDT against F. monophora remains poorly documented. In the present work, ALA (5-Aminolaevulinic Acid) was employed as photosensitizer and a LED device was served as light source to investigate photodynamic effect on F. monophora conidia under different ALA-PDT conditions in a direct way. RAW264.7 was stimulated by conidia treated with ALA-PDT to study the photodynamic effect on F. monophora conidia in an indirect way. It was observed that ALA-PDT can inactivate F. monophora conidia directly in a concentration-dependent and dose-dependent manner. RAW264.7 was activated indirectly by photodynamically treated conidia. ALA-PDT can enhance the fungicidal ability of RAW264.7 and protect it from Infection-induced apoptosis in an indirect way. ROS generated by photodynamic treated conidia is associated with mitochondrial-related apoptosis in RAW264.7.The results of this investigation demonstrated that ALA-PDT inactivate F. monophora through two way: directly killing F. monophora conidia through ROS-dependent Oxidative damage; activating RAW264.7 in an indirect way.