Paracoccidioidomycosis (PCM) is a systemic mycosis caused by thermally dimorphic
fungi of the genus
Paracoccidioides that
affects predominantly 30-60-year-old
male rural workers . The main clinical forms of the
disease are acute/subacute, chronic (CF); almost all CF
patients develop
pulmonary fibrosis , and they also exhibit
emphysema due to
smoke . An important
cytokine in this context,
IL-1 ß, different from the others, is produced by an intracellular multimolecular complex called
inflammasome that is activated by pathogens and/or host signs of damage.
Inflammasome has been recognized for its contribution to chronic inflammatory
diseases , from that, we hypothesized that this activation could be involved in
paracoccidioidomycosis , contributing to chronic
inflammation . While
inflammasome activation has been demonstrated in
experimental models of
Paracoccidioides brasiliensis infection , no information is available in
patients , leading us to investigate the participation of NLRP3-
inflammasome machinery in CF/PCM
patients from a Brazilian endemic area. Our findings showed increased priming in
mRNA levels of NLRP3
inflammasome genes by
monocytes of PCM
patients in vitro than healthy controls.
Similar intracellular
protein expression of NLRP3, CASP-1, ASC, and
IL-1 ß were also observed in freshly isolated
monocytes of PCM
patients and
smoker controls. Increased expression of NLRP3 and ASC was observed in
monocytes from PCM
patients under
hypoxia in comparison with
smoker controls. For the first
time , we showed that primed
monocytes of CF-PCM
patients were associated with enhanced expression of components of NLRP3-
inflammasome due to
smoke . Also,
hypoxemia boosted this
machinery . These findings reinforce the systemic low-grade
inflammation activation observed in PCM during and
after treatment .