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INVOLVEMENT OF TLR4 AND PPAR‐α RECEPTORS IN HOST RESPONSE AND NLRP3 INFLAMMOSOME ACTIVATION, AGAINST PULMONARY INFECTION WITH PSEUDOMOSAS AERUGINOSA
Author(s) -
GUGLIANDOLO ENRICO,
Fusco Roberta,
Ginestra Giovanna,
D'amico Ramona,
Bisignano Carlo,
Mandalari Giuseppina,
Cuzzocrea Salvatore,
Di Paola Rosanna
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.832.9
Subject(s) - tlr4 , tlr2 , innate immune system , proinflammatory cytokine , receptor , pattern recognition receptor , inflammasome , immunology , inflammation , immune system , toll like receptor , biology , biochemistry
Background Colonization with Pseudomonas aeruginosa (PA), the most common pathogen isolated mainly in patients with cystic fibrosis, is particularly difficult to eradicate and is associated with acceleration of decline in lung function and with poorer prognosis. Host resistance to PA is dependent on the activation of an innate immune response. The initiation of this response requires the recognition of bacterial ligands by signaling receptors. Recently, Toll‐like receptors (TLRs) have been found to have prominent roles in the activation of innate immune responses to infection. PA LPS is recognized by TLR4 and has been shown to induce lung inflammation in vivo . In addition, regulation of this process is essential for proper pathogen clearance and to prevent excessive inflammatory response resulting in tissue damage. This occurs through the production of different cytokines, and the activation of different pathways such as inflammasome activation, which is responsible for the production of IL‐1b. Moreover the airway epithelial cells respond with increased production of proinflammatory cytokines as a result of increased NF‐κB activation. One potential regulator of NF‐κB activation are the peroxisome proliferator‐activated receptors (PPARs), and PPARa is a member of the ligand‐activated nuclear receptor superfamily. Thus, the purpose of the present study was to evaluate the role of TLR4 and PPARa in the pulmonary innate immunity response to PA and in the consequent inflammatory response. Methods To evaluate the involvement of TLR4 and PPARa in a PA infection, we used TLR4 KO and PPARa KO mice who received an intratracheal (i.t.) administration of 50 ml of PA strain (106 CFU), thus evaluating if these mice were profoundly susceptible to PA compared to WT mice. Results The results of the present study showed that administration of PA worsened the pathophysiology of PA lung disease in TLR4 and PPARa KO mice compared to WT. Conclusions The present study demonstrated that TLR4 and PPARa receptors would mediate the earliest control of bacterial replication as well as proinflammatory responses to PA infections, and in particular that PPARa receptors are needed to prevent an excessive inflammatory response, as in the control of the inflammosome complex NLP3 activation. Support or Funding Information no funding This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .