The role of Caspase 1 inflammasome and IL-18 during colonization infection

Ref ID: 19589

Author:

B Ralph1,2*, M Lehoux1,2, B Snarr1,2, M Saleh1,2, D Sheppard1,2

Author address:

1Microbiology and Immunology, McGill University, Montreal, Canada
2Reasearch Instute of McGill University Health Centre, Montreal, Canada

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose:
Patients with chronic lung disease such as cystic fibrosis, are commonly colonized by Aspergillus
fumigatus. While a minority of these patients will develop allergic bronchopulmonary aspergillosis
(ABPA), even in the absence of ABPA Aspergillus colonization is associated with increased numbers
of pulmonary exacerbations and declining lung function. The inflammatory response to colonization
with A. fumigatus hyphae in the absence of ABPA is poorly understood. We hypothesized that the
inflammasome may play an important role in governing the host response to airway colonization
with A. fumigatus.
Methods:
Mice were injected intratracheally with agar beads embedded with A. fumigatus conidia. Fungal
galactomanan content in the lung was quantified as a measure of disease progression. Host immune
response was measured by leukocyte recruitement and cytokine profile by EIA.
Results:
Our initial studies found that pulmonary colonization was associated with increased pulmonary
levels of IL-1β in wild type B6 mice. Caspase 1 is the canonical protease responsible for pro8209;IL8209;1β ,
we therefore investigated the outcome of an infection in caspase 1 deficient mice. Caspase 1 deficient
mice were found to be hyper-susceptible to fungal colonization and displayed an increased in fungal
burden during the first week of infection. Interestingly, this increased fungal burden was associated
with normal levels of IL-1β but decreased levels of IL-18, and increased levels of neutrophil
recruitment.
Conclusion:
These results suggest that the caspase-1 inflammasome mediates protection against fungal infection
in an IL-1β -independent fashion and that IL-1β processing during hyphal colonization is mediated
by a non-canonical caspase 1 independent pathway. Further we hypothesize that IL-18 processing
by caspase 1 plays a role in controlling the infection.

Abstract Number: 114

Conference Year: 2014

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

New link: NULL

Conference abstracts, posters & presentations

Showing 10 posts of 17325 posts found.

  • Title

    Author

    Year

    Number

    Poster