Role of Lipoxygenase During Experimental Infection with Cryptococcus deuterogattii

Arachidonic acid is present in the phospholipids of the cell membrane and is released following the activation of phospholipase A2. Immediately after its release, arachidonic acid is subsequently metabolized through various enzymatic and non-enzymatic pathways, such as the cyclooxygenase (COX) and lipoxygenase (LOX) pathways. Lipoxygenases catalyze the formation of hydroperoxides as the first step in the biosynthesis of several inflammatory mediators. LOX enzymes are expressed in immune, epithelial, and tumor cells and have a variety of physiological functions, including inflammation. In the context of fungal infection, lipoxygenases play an important role in the immune response by producing pro-inflammatory mediators in the activation of antifungal immunity, such as leukotrienes, and anti-inflammatory mediators, such as lipoxins, to preserve adjacent tissues. Therefore, the effect of the absence of LOX during infection with the fungus Cryptococcus deuterogattii (R265) was studied using two groups of SV129 mice: one group wild-type (WT) and the other Knock-Out (KO) for LOX. The animals were monitored for 3 weeks, with observations on survival, clinical score, weight, fungemia, and colony-forming units in organs (lung, lymph node, brain, and spleen). Additionally, pro-inflammatory cytokines IL-17A and IL-6 were analyzed. The results showed that LOX KO animals exhibited greater survival, lower clinical scores, and less weight loss. Moreover, fungal load was lower in the organs of KO animals compared to WT infected mice, indicating that LOX-deficient animals better control the infection. Furthermore, there was increased production of IL-6 and IL-17A in the lungs of LOX KO animals, as well as a higher immune cell infiltrate in the same group, suggesting enhanced activation of antifungal immunity in these animals. Therefore, lipoxygenase may be involved in regulating the inflammatory response and pathogenesis of pulmonary cryptococcosis.