Abstract

ABSTRACTAspergillus flavus is liable to mediate immune response in a wide variety of cells by inducing varied host pathogen interactions, being the most etiological agent in India. The culture filtrate and spores of fungal species are implicated in the onset of allergic responses finally leading to the initiation of proinflammatory reactions. Human monocytic U937 cells were exposed to varying concentrations of culture filtrate and spores as well, to establish their cytotoxic role and proinflammatory effect. The expression of a wide array of proinflammatory cytokines, particularly interleukin-8 (IL-8), was found to be induced in a dose-dependent manner upon stimulation of cells. The upregulation of cytokine IL-8 was further shown to be associated with the regulation of signalling pathways mediated via p38 and one of its prime downstream target molecules, activator protein-1 (AP-1) transcription factor. The p38 mitogen-activated protein kinase (MAPK) signalling pathway regulates the transcription factor AP-1 activity, the integration point of many signals that can differentially affect the expression and transcriptional activity of a cell. We observed activation of c-Jun, a critical component of the AP-1 complex, mediated by p38 MAPK upon stimulation with the culture filtrate. Thus, this study showed a crucial role of culture filtrate and spores of A. flavus in mediating the immune responses by the secretion of proinflammatory cytokines.Abbreviations IL-8, Interleukin-8; TNF α, Tumor necrosis factor alpha; GM-CSF, Granulocyte macrophage colony stimulating factor

Highlights

  • Aspergillus flavus, a pervasive and inescapable pathogenic fungus, lies next to A. fumigatus in causing invasive as well as non-invasive pulmonary aspergillosis in immunocompetent persons (Denning 1998; Sharon et al 2011)

  • In order to verify whether A. flavus has any cytotoxic effect on the cells, we measured the release of the cytosolic enzyme lactate dehydrogenase (LDH) into the supernatant after 6 and 12 h of stimulation with varying concentrations of the culture filtrate in U937 cells

  • From the last few decenniums, an active field of research was intent to figure out the effect of fungal pathogens on cells paving a way to numerous host pathogen interactions which results in the secretion of cytokines and activates major signalling pathways

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Summary

Introduction

Aspergillus flavus, a pervasive and inescapable pathogenic fungus, lies next to A. fumigatus in causing invasive as well as non-invasive pulmonary aspergillosis in immunocompetent persons (Denning 1998; Sharon et al 2011). Fungi are capable enough to endure in dynamic habitats by sensing their environs and retorting to cues in the particular habitat they live in through means of interaction with plants, animals or humans in multifaceted approaches, thereby establishing a range of host pathogen interactions. This involves particular reprogramming events which in turn facilitates them to become accustomed to the ecological conditions, struggle for nutrient acquirement and cope with the stress generated by host defence mechanisms (Romani 2004; Hube 2009). In adenocarcinomic human alveolar basal epithelial cells, A549, the Published online 12 Apr 2017

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