Abstract
Novel role for inflammasome-dependent IL-18 in promoting Th2 responses during Leishmania infections (IRC7P.420)
The Journal of immunology (1950), Vol.194(1_Supplement), pp.128-128.1
05/01/2015
DOI: 10.4049/jimmunol.194.Supp.128.1
Abstract
Abstract Leishmaniasis is a global health disease and is categorized under neglected tropical disease by WHO. Despite tremendous amount of economic burden and morbidity and mortality associated with Leishmania infections, studies to understand these parasitic bugs are nevertheless lacking. As a result, specific targeted treatment options or vaccines to treat Leishmaniasis are still missing. Herein, we sought to understand how inflammasomes are involved in host responses during Leishmania major infection. One of the hallmarks of inflammasome is the activation of caspase-1 and ultimate release of bioactive IL-1β and IL-18. Interestingly, we found that mice lacking components of the NLRP3 inflammasome were resistant to L. major infections in comparison to their WT counterparts. Using in vitro and in vivo approaches, we showed that L. major activates NLRP3 inflammasome. We further demonstrated that NLRP3 inflammasome induced IL-18, but not IL-1β, promoted Th2 responses during L. major infection. Mechanistically, IL-18 enhanced expression of Th2 transcription factors GATA3 and cMAF in T cells. Finally, we were able to show that IL-18 neutralization in WT mice protected from L. major infections. In conclusion, our study uncovered a novel role for inflammasome-induced IL-18 in promoting Th2 responses and Leishmaniasis, which can potentially be targeted for therapeutic benefits during L. major infections.
Details
- Title: Subtitle
- Novel role for inflammasome-dependent IL-18 in promoting Th2 responses during Leishmania infections (IRC7P.420)
- Creators
- Prajwal Gurung - St. Jude Children's Research HospitalThirumala-Devi Kanneganti - St. Jude Children's Research Hospital
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.194(1_Supplement), pp.128-128.1
- DOI
- 10.4049/jimmunol.194.Supp.128.1
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2015
- Academic Unit
- Infectious Diseases; Internal Medicine
- Record Identifier
- 9984362351702771
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