Differential Upregulation of Surface Dectin -1 Expression on Sputum Neutrophils in CF-ABPA

Ref ID: 19607

Author:

Y Gernez1, J Waters1, C Everson2, C Hernandez2, LA Herzenberg1, RB Moss3*

Author address:

1Genetics, Stanford University School of Medicine, Stanford, USA
2The Cystic Fibrosis Center at Stanford, Stanford Medicine, Stanford, USA
3Pediatrics, Stanford Medicine, Stanford, USA

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Introduction:
A. fumigatus (Af) colonizes the airways of 25-50% of cystic fibrosis (CF) patients, with some
further progressing to allergic bronchopulmonary aspergillosis (ABPA). Even if multiple genetic/
environmental factors likely determine susceptibility of CF patients (~10%) to develop ABPA, it is
still not well understand why most CF patients colonized by Af do not develop ABPA while some
do. Polymorphonuclear neutrophils (PMN), essential actors in the innate response to Af hyphae, can
recognize Af via pattern recognition receptors such as dectin-1 and its cognate fungal ligand b-glucan.
Dectin-1 has been shown to regulate exocytosis and other PMN functions. We hypothesized that
the expression of dectin-1 at the surface of sputum PMN in CF-ABPA patients would be higher
compared to CF patients without ABPA, whether chronically colonized with Af or not.
Method:
We present results from a longitudinal cohort study here comparing blood and sputum PMN dectin-1
levels. Cell surface dectin-1 was measured by flow cytometry on freshly isolated PMN without any
in vitro activation in 10 CF-ABPA patients and two control groups: CF patients colonized with Af
but without ABPA (CF-AC; n=10), and CF patients without Af colonization or ABPA (CF; n=14).
The overall goals of this longitudinal study are to evaluate the interactions between Af and innate
immune cells in CF blood and airways as accessed via induced sputum.
Results:
In all three CF groups, surface dectin-1 levels were increased on sputum PMN as compared to
their blood counterparts (CF-ABPA: p=0.0035; CF-AC; p<0.001 and, CF, p<0.001). Furthermore, in sputum, surface PMN dectin-1 levels showed a trend toward increase in CF-ABPA patients compared to CF-AC (+128%, p=0.29) and CF patient groups (+112%, p=0.39). In our cohort CFABPA patients experienced more pulmonary exacerbations, were more frequently co-infected with P. aeruginosa, and had more diabetes than controls. In contrast, co-infection with S. aureus or S. maltophilia was similar in CF-ABPA and controls. Conclusion: CF-ABPA patients are distinguished from CF patients without ABPA (whether chronically colonized by Af or not) by ongoing innate immune activation as manifested by upregulated blood basophil surface CD203c (Gernez et al, JCF 2012; 11:502-10; Moss et al, JCF 2013; 12:S46). Additionally we show here that sputum but not blood PMN show an upregulation of dectin-1 as another feature of this innate response, which may be differentially increased in ABPA. Further patients will have to be enrolled to clearly evaluate this last finding.

Abstract Number: 132

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

New link: NULL

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