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Volume 8, Issue 3 (Suppl)
J Clin Cell Immunol, an open access journal
ISSN: 2155-9899
Euro Immunology 2017
June 29-July 01, 2017
June 29-July 01, 2017 Madrid, Spain
8
th
European
Immunology Conference
NLRP3-inflammassome participates in the inflammatory response induced by
Paracoccidioides brasiliensis
Barbara Soares Gonçalves, Eduardo Kanagushiku Pereira, Frank Gregory Cavalcante da Silva, Ana Lúcia Bergamasco Galastri
and
Ronei Luciano Mamoni
Faculty of Medicine of Jundiaí, Brazil
S
everal studies have shown that the inflammatory response is crucial for the control of paracoccidioidomycosis (PCM); however,
exacerbation of inflammation leads to tissue damage and imbalance of the acquired immune response. The inflammatory response
initiates after the recognition of pathogens by receptors expressed by innate immune cells. Among these receptors, the NLRP3 was
associated with the recognition of pathogenic fungi in experimental models. NLRP3 operates forming a multi-proteic complex
called inflammasome, which actives caspase-1, responsible for the production of the inflammatory cytokines IL-1beta and IL-18.
In this study, we aimed to investigate the involvement of NLRP3 in the inflammatory response elicited in macrophages against
Paracoccidioides brasiliensis
(Pb), the etiologic agent of PCM. Macrophages were differentiated from THP-1 cells by treatment with
phorbol-myristate-acetate. Following differentiation, macrophages were stimulated by Pb yeast cells for 24 hours, after previous
treatment with specific NLRP3 (3, 4-methylenedioxy-beta-nitrostyrene) and/or caspase-1 (VX-765) inhibitors, or specific inhibitors
of pathways involved in NLRP3 activation such as: Reactive Oxygen Species (ROS) production (N-Acetyl-L-cysteine), K+ efflux
(Glibenclamide) or phagosome acidification (Bafilomycin). Quantification of IL-1beta and IL-18 in supernatants was performed
by ELISA. Our results showed that the production of IL-1beta and IL-18 by THP-1-derived-macrophages stimulated with Pb yeast
cells was dependent on NLRP3 and caspase-1 activation, once the presence of their specific inhibitors diminished the production of
these cytokines. Furthermore, we found that the major pathways involved in NLRP3 activation, after Pb recognition, were dependent
on ROS production and K+ efflux. In conclusion our results showed that NLRP3 participates in the recognition of Pb yeast cells by
macrophages, leading to the activation of the NLRP3-inflammasome and production of IL-1beta and IL-18. Together, these cytokines
can induce an inflammatory response against
P. brasiliensi
s, essential for the establishment of the initial inflammatory response and
for the development of the subsequent acquired immune response.
bsg.goncalves@gmail.comJ Clin Cell Immunol 2017, 8:3(Suppl)
DOI: 10.4172/2155-9899-C1-037