Galactomannan Downregulates the Inflammation Responses in Human Macrophages via NFκB2/p100.

Víctor Toledano,Enrique Hernández-Jiménez,Aníbal Varela-Serrano,Francisco García-Rio,Carolina Cubillos-Zapata,Eduardo López-Collazo,Ramón Cantero,Marta Flandez,Gema Valles,Enrique Álvarez

doi:10.1155/2015/942517

Víctor Toledano, Enrique Hernández-Jiménez + Show 8 more

Open Access

https://doi.org/10.1155/2015/942517

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Abstract

We show that galactomannan, a polysaccharide consisting of a mannose backbone with galactose side groups present on the cell wall of several fungi, induces a reprogramming of the inflammatory response in human macrophages through dectin-1 receptor. The nuclear factor kappa-light-chain-enhancer of activated B cells 2 (NFκB2)/p100 was overexpressed after galactomannan challenge. Knocking down NFκB2/p100 using small interfering RNA (siRNA) indicated that NFκB2/p100 expression is a crucial factor in the progression of the galactomannan-induced refractoriness. The data presented in this study could be used as a modulator of inflammatory response in clinical situations where refractory state is required.

Highlights

Galactomannan (GAL) is a component of the cell wall of several fungi and is released during growth [1]
It is well accepted that human monocytes and macrophages (MΦs) preconditioned with endotoxins, mitochondrial Danger Associated Molecular Patterns (DAMPs), or some tumor cells are unable to orchestrate a classic inflammatory response once they are challenged with LPS [8, 14, 15, 22]
This phenomenon has been described in patients that suffered from sepsis, acute coronary syndrome (ACS), and chronic lymphocytic leukemia (CLL), in which their circulating cells were unable to produce inflammation after an ex vivo endotoxin challenge [15, 24, 31]

Summary

Introduction

Galactomannan (GAL) is a component of the cell wall of several fungi and is released during growth [1]. Detection of GAL in blood is used to diagnose invasive fungal infections [2, 3]. Several studies have demonstrated invasion by fungi occurring primarily in the setting of immunosuppression or during refractory states [4, 5]. With normal immune function prior Intensive Care Unit admission, developed a refractory status and, subsequently, an invasive pulmonary aspergillosis [6]. We have generalized a refractory state caused by the presence of bacteria which may lead to the invasion of fungal infections. There are not data on the potential effect of fungi invasion on the modulation of the innate immune response

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