Role of NOD receptors in the host defence against Aspergillus fumigatus

Ref ID: 19365

Author:

M. Gresnigt1 M. Oosting,2 D. J. de Jong,3 L.A.B. Joosten,2
T. D. Kanneganti,4 M. G. Netea2 and F. L. van de Veerdonk

Author address:

1Radboud University Nijmegen Medical Centre, the Netherlands;
2 Department of Medicine, Radboud University Nijmegen Medical
Centre, the Netherlands; 3 Department of Gastroeterology,
Radboud University Nijmegen Medical Centre, the Netherlands
and

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Objectives Humans are ubiquitously exposed to Aspergillus, but
only immunocompromised hosts are at risk of developing life-
threatening infections. Polymorphisms with functional conse-
quences in genes involved in the immune system could explain
why some patients are even more at risk than others to develop
invasive aspergillosis. There is increasing evidence that the intra-
cellular pattern recognition receptor nucleotide-binding oligomeriza-
tion domain (NOD)2 receptor plays a role in the host defense
against Aspergillus. Therefore our objective was to identify whether
polymorphisms in NOD receptors influence the host response
against A. fumigatus.
Methods Human peripheral blood mononuclear cells (PBMCs) iso-
lated from donors with single nucleotide polymorphisms in NOD2 or NOD1, and splenocytes isolated from wildtype, NOD1-/- and NOD2-/-
mice were stimulated were stimulated with Aspergillus and cytokines
were measured in the supernatants by ELISA.
Results PBMCs with polymorphisms in NOD2, respond with both
decreased innate cytokine, (TNFa IL-1b and IL-6) and Th cytokine
(IL-17, IL-22 and IFNc) production in response to A. fumigatus stimu-
lation, whereas an insertion deletion polymorphism in NOD1 resulted
in an increased Aspergillus-induced TNFa, IL-6 and IL-1b responses.
In addition, NOD2-/- splenocytes responded with a decreased IL-6,
TNFa and KC response to Aspergillus-stimulation compared to wild-
type splenocytes, whereas NOD1-/- splenocytes responded with
increased TNFa and KC responses and slightly increased IL-1b and
IL-6 responses. Compared to wildtype, NOD1-/- also demonstrated sig-
nificantly increased IL-17, IL-22 and IFNc production in response to
Aspergillus stimulation.
Conclusion Collectively, our data provide novel insight in how the
intracellular NOD receptors play a role in induction cytokine produc-
tion in response to Aspergillus. On the one hand NOD2 is required for
induction of proinflammatory cytokine production by innate and
adaptive immune cells, while on the other hand the investigated
NOD1 polymorphism results in increased Aspergillus-induced cytokine
responses. These observations suggest that Aspergillus-induced cyto-
kine responses are differentially dependent on both the NOD1 and
NOD2 pathway.

Abstract Number: o3.2

Conference Year: 2013

Link to conference website: NULL

New link: NULL

Conference abstracts, posters & presentations

Showing 10 posts of 17325 posts found.

  • Title

    Author

    Year

    Number

    Poster