THE ROLE OF PTX3 IN INNATE REGULATION OF ANTIFUNGAL IMMUNITY IN CHRONIC PULMONARY ASPERGILLOSIS

Author:

C Duarte-Oliveira1,2, S Ferreira1,2, SM Gonçalves1,2, D Antunes1,2, A Mantovani3,4,
C Cunha1,2, A Carvalho1,2

Author address:

1Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal
2ICVS/3B’s – PT Government Associate Laboratory, University of Minho, Braga/Guimarães, Portugal
3Humanitas Clinical and Research Center, Humanitas Clinical and Research Center, Rozzano (Milan), Italy
4Humanitas University, Humanitas University, Rozzano (Milan), Italy

Full conference title:

9th Advances Against Aspergillosis

Date: 27 February 2020

Abstract:

Purpose: Chronic pulmonary aspergillosis (CPA) is an infection with devastating consequences to the lungs, especially for the expanding population of chronic obstructive pulmonary disease (COPD) patients. Susceptibility to CPA differs significantly even among patients with similar predisposing conditions, but the mechanisms that influence the efficacy of individual antifungal immune responses remain almost unknown. Among the many molecules endowed with regulatory properties of antifungal immune responses, the soluble pattern recognition receptor pentraxin-3 (PTX3) has been demonstrated to play a non-redundant role during infection with the fungal pathogen Aspergillus fumigatus. In immunocompromised hosts, genetic variants impairing the expression of PTX3 renders carriers highly susceptible to invasive aspergillosis. Whether PTX3 also influences susceptibly to chronic forms of aspergillosis in otherwise immunocompetent individuals remains unknown. 

Methods: Here, we have analyzed the contribution PTX3 to antifungal immunity, using a mouse model of CPA based on agar beads containing fungal conidia that trigger the formation of fungal granulomas in the lungs.

Results: Using this model, we found that PTX3 is readily induced upon infection in the lungs and that its expression is required for the control of disease. Indeed, contrary to wild-type mice, Ptx3-deficient animals rapidly succumb to infection, a finding in line with the higher fungal burden detected in the lungs. Mechanistically, Ptx3-deficient macrophages were found to display impaired antifungal effector functions

Conclusion: Collectively, these results highlight the requisite role of PTX3 to antifungal immunity and establish PTX3 as an attractive target for immunotherapeutic strategies to prevent or treat CPA.

Abstract Number: 177

Conference Year: 2020

Link Conference abstract: 

AAAM 2020

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