Studies on the release of neutrophil extracellular traps and IFN-γ as part of the innate immune response to Aspergillus fumigatus and on the fungal stress response via the hybrid sensor kinase TcsC

摘要: Aspergillus fumigatus is a saprophytic mold that naturally inhabits the soil. Asexual reproduction yields hardy conidia circulate in air and are inhaled daily by humans. The fungus seems not to have evolved distinct mechanisms of pathogenicity, but capable responding many stressful environmental cues present its harsh niche. robust no problem fully functioning immune system, if innate system compromised, can become activated differentiate within lung tissue form invasive disseminating hyphae. resulting disease called aspergillosis difficult detect treat. To date, scientists yet find factor(s) missing during immunosuppression allow healthy patient easily dispose A. fumigatus. We explored two possibilities: production neutrophil extracellular traps (NETs) release IFN-γ natural killer (NK) cells. report here NETs alone cannot kill fungus, do inhibit polar growth. Elongation hyphal tips abrogated due zinc starvation, likely consequence zinc-chelating, NETs-associated protein calprotectin. NK cells also incapable fungicidal activity, their upon contact with abrogates growth unknown mechanism. In vitro studies response, though helpful, far from representative vivo response. Neither nor manage infection, combination, these other assaults certainly can. difficulty lies identifying precise combination cytokine milieu individual prevent infection. Additionally, we which responds stress, namely HOG MAPK pathway, historically involved osmotic stress filamentous fungi, certain signals sensed cytoplasmic hybrid histidine kinase sensor then passed through via phosphorylation. identified putative fumigatus, generated corresponding knockout mutant. ΔtcsC mutant was indeed sensitive resistant phenolpyrrole fungicide fludioxonil. wild type addition either or fludioxonil resulted SakA phosphorylation translocation nucleus. SakA, Hog1 homolog located at end confirming role TcsC as upstream SakA. hypoxia, on farnesol, high concentrations divalent cations exhibited striking “fluffy” phenotype characterized tremendous aerial hyphae little differentiation, i.e., conidiation. Though showed change virulence compared type, components signalling pathway remain promising targets for antifungal agents.