Anti-pyocyanin Antibody Exhibits Cytotoxicity Protective Effects on Macrophages: A Promising Innovative Therapeutic Approach for <i>Pseudomonas aeruginosa</i> Infections

<i>Pseudomonas aeruginosa</i> is considered one of the most threatening pathogens worldwide, due to its high adaptability, which leads to resistance to classical antimicrobials. This fact has driven the development of new therapeutic strategies to reduce multiresistant strains and to minimize infection progression. In this context, the protective effect of a monoclonal antibody (mAb122) specific to pyocyanin (PYO), a key virulence factor of <i>P. aeruginosa</i>, was studied <i>in vitro</i>. Quenching PYO may reduce <i>P. aeruginosa</i> pathogenesis and partially lessen host immune dysregulation by impairing cytokine production. With this aim, murine macrophages were challenged with different PYO concentrations to assess their cytotoxicity by evaluating different cell viability hallmarks. Subsequently, the protective effect of mAb122 was studied on the PYO-treated cells. The addition of mAb122 significantly increased the percentage of viable cells compared to those treated just with the virulence factor (4.34- to 11.07-fold increase in MH-S and RAW 264.7 cells, respectively). Moreover, the PYO immunomodulatory effect and the outcome of mAb122 addition on the host response were also studied by measuring relevant cytokines in cell media. Results showed that mAb122 treatment, rather than reversing PYO impairment in cytokine production, either maintained the levels or triggered an increase, depending on the specific cytokine examined. Thus, the significant rise in cell viability and the nontoxic effect of mAb122 itself <i>in vitro</i> place PYO mAb as a promising candidate for <i>in vivo</i> testing as a potential therapeutic agent. However, its effects on the host immune system should be carefully studied and minimized.