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Conceived and designed the experiments: Received Jul 12; Accepted Jan 5. This article has been cited by other articles in PMC. Abstract The galactosaminogalactan GAG is a cell wall component of Aspergillus fumigatus that has potent anti-inflammatory effects in mice. However, the mechanisms responsible for the anti-inflammatory property of GAG remain to be elucidated.
Additionally, we demonstrate that the capacity of GAG to induce IL-1Ra could also be used for treatment of inflammatory diseases, as GAG was able to reduce severity of an experimental model of allergic aspergillosis, and in a murine DSS-induced colitis model.
In the setting of invasive aspergillosis, GAG has a significant immunomodulatory function by inducing IL-1Ra and notably IL-1Ra knockout mice are completely protected to invasive pulmonary aspergillosis.
This opens new treatment strategies that target IL-1Ra in the setting of acute invasive fungal infection. Author Summary Aspergillus fumigatus is an opportunistic pathogenic fungus that primarily causes infections in the immunocompromised host. It is known that Aspergillus employs various strategies to evade immune recognition by the host's immune system.
Recently, galactosaminogalactan GAGa new component of the Aspergillus cell wall, was discovered to have potent anti-inflammatory effects in mice making them more susceptible to Aspergillosis.
In the current study we found that this anti-inflammatory property of GAG was due to its capacity to induce the potent anti-inflammatory cytokine interleukin-1 Receptor antagonist.
This cytokine interferes with IL-1 signalling and thereby can reduce IL-1—induced immune responses such as T-cell responses. We also found that the induction of this anti-inflammatory cytokine by GAG correlates with increased fungal burden, and mice deficient for this cytokine were protected against aspergillosis.
Additionally, we show that the capacity of GAG to induce the natural regulator of IL-1 signalling could be used in the treatment of IL-1—mediated disease such as allergy and colitis. Our study provides new insights on the immunoregulatory activity of GAG and opens up possibilities to exploit the anti-inflammatory potential of GAG as a therapy for inflammatory diseases.
Introduction Aspergillus fumigatus is an opportunistic fungus that causes infections under specific conditions, of which secondary immunodeficiency is by far the largest risk factor for the development of invasive infections .
In order to initiate an effective host response against Aspergillus, recognition of conserved pathogen associated molecular patterns PAMPs by specific pattern recognition receptors PRRs is required.
Some of these polysaccharides are recognized by various PRRs expressed on human immune cells . Rodlets and melanin, that are present on the conidial surface, shield PAMPs that elicit pro-inflammatory host responses .
Another cell wall component of A. GAG is not expressed on Aspergillus conidia, but is exposed when conidia start to germinate and was found to be present in the extracellular matrix that surrounds Aspergillus hyphae in aspergilloma isolated from patients and in experimental murine invasive aspergillosis .
This polysaccharide that is shed into the host environment during Aspergillus vegetative growth induces immunosuppressive effects that results in diminished neutrophil recruitment, which predisposes mice to A.
However, the mechanism through which GAG induces immunosuppressive effects as well as its capacity to induce similar immunosuppressive effects on the human immune response were unknown. Therefore, we investigated whether GAG can be immunosuppressive in the human host response against A.
Thus, GAG can inhibit human proinflammatory Th cytokine production induced by Aspergillus and cytokine cocktails.Aspergillus fumigatus is an environmental filamentous fungus that also acts as an opportunistic pathogen able to cause a variety of symptoms, from an allergic response to a life-threatening disseminated fungal infection.
The infectious agents are inhaled conidia whose first point of contact is most likely to be an airway epithelial cell (AEC).
This is a series of HE and PAS stained slides demonstrating intra-sinus inflammation and fungal structures with Aspergillus fumigatus in the rabbit. inflammatory response to inhale d Aspergillus conidia.
At the same time, the staged inflammatory response to the fungus may represent a selec tive mechanism to. Paper Critique: Aspergilla’s Fumigatus Anti-inflammation The study reconnoitred the possible techniques to extract and test whether a component of the cell wall of the fungus; aspergilla’s fumigatus .
THIS paper is a retrospective study of thirty-nine patients with lung disease, caused by aspergillus fumigatus, seen in two large general hospitals over a ten year period. A Polysaccharide Virulence Factor from Aspergillus fumigatus Elicits Anti-inflammatory Effects through Induction of Interleukin-1 Receptor Antagonist.