Immunological relevance of the mammalian receptor G2A in the host response to Aspergillus fumigatus pulmonary infection

Author:

BN Steffan1*, DG Calise1, NP Keller1,2

Author address:

1Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA

2Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA

Full conference title:

10th Advances Against Aspergillosis and Mucormycosis

Date: 2 February 2022

Abstract:

Purpose:

Aspergillus fumigatus is the main causative infectious agent of invasive aspergillosis, a fungal infection with up to 90% mortality. Understanding the immunological mechanism behind the initiation and establishment of fungal growth within the lung is still widely unknown. An area of increasing interest is in the role of oxygenated fatty acid (oxylipin) signaling in disease pathogenesis. G2A is a vertebrate GPCR with known oxylipin ligands including 9-HODE and 13-HODE. The absence of G2A in inflammatory diseases, including infections, results in altered immune cell recruitment, polarization, and cytokine production. We hypothesize that G2A plays a critical role in the establishment of infection by A. fumigatus through altered inflammatory processes resulting in more critical disease outcomes.

 

Methods:

Immunocompetent G2A+/+ and G2A-/- mice were infected with A. fumigatus (CEA10) intranasally and monitored for ten days for survival. An early timepoint (D1 pi) was chosen to assess changes to immune cell egress (flow cytometry) to the lungs, fungal burden, and cytokine/chemokine production (ELISA) from bronchoalveolar lavage.

 

Results:

G2A-/- mice were less likely to succumb to death upon infection in comparison to G2A+/+ mice. Both groups showed increased neutrophilia at D1 pi, with a trend toward more neutrophils in the G2A-/- animals. However, G2A-/- mice had a significantly lower percent population of CD11b+CD11c- macrophages in comparison to G2A+/+ mice. IL-6 production is significantly higher in G2A-/- mice at D1 pi when compared to G2A+/+ mice.

 

Conclusions:

Immune responses to A. fumigatus are more effective at preventing infection-related mortality when G2A is absent in comparison to G2A+/+ animals. Changes in IL-6 production and immune cell egress to the lungs in G2A-/- mice are likely critical to disease development and will be explored further in future studies.

Abstract Number: 72

Conference Year: 2022

Link to conference website: https://aaam2022.org/

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