Aerosolized Harmful Algal Bloom Toxin Microcystin-LR Induces Type 1/Type 17 Inflammation of Murine Airways

• Published in: Toxins Vol. 16; no. 11; p. 470
• Main Authors: Breidenbach, Joshua D., French, Benjamin W., Stanoszek, Lauren M., Lavik, John-Paul, Maddipati, Krishna Rao, Premathilaka, Sanduni H., Baliu-Rodriguez, David, Timalsina, Bivek, Aradhyula, Vaishnavi, Patel, Shivani C., Lad, Apurva, Syed, Irum, Kleinhenz, Andrew L., Blomquist, Thomas M., Gohara, Amira, Dube, Prabhatchandra, Zhang, Shungang, Faleel, Dhilhani, Khalaf, Fatimah K., Isailovic, Dragan, Wooten, R. Mark, Willey, James C., Hammersley, Jeffrey R., Modyanov, Nikolai N., Malhotra, Deepak, Dworkin, Lance D., Kennedy, David J., Haller, Steven T.
• Format: Journal Article
• Language: English
• Published: 01.11.2024
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins16110470

Harmful algal blooms are increasing globally and pose serious health concerns releasing cyanotoxins. Microcystin-LR (MC-LR), one of the most frequently produced cyanotoxins, has recently been detected in aerosols generated by the normal motions of affected bodies of water. MC-LR aerosol exposure has been linked to a pro-inflammatory influence on the airways of mice; however, little is understood about the underlying mechanism or the potential consequences. This study aimed to investigate the pro-inflammatory effects of aerosolized MC-LR on murine airways. C57BL/6 and BALB/c mice were exposed to MC-LR aerosols, as these strains are predisposed to type 1/type 17 and type 2 immune responses, respectively. Exposure to MC-LR induced granulocytic inflammation in C57BL/6 but not BALB/c mice, as observed by increased expression of cytokines MIP-1α, CXCL1, CCL2, and GM-CSF compared with their respective vehicle controls. Furthermore, the upregulation of interleukins IL-17A and IL-12 is consistent with Th1- and Th17-driven type 1/type 17 inflammation. Histological analysis confirmed inflammation in the C57BL/6 lungs, with elevated neutrophils and macrophages in the bronchoalveolar lavage fluid and increased pro-inflammatory and pro-resolving oxidized lipids. In contrast, BALB/c mice showed no significant airway inflammation. These results highlight the ability of aerosolized MC-LR to trigger harmful airway inflammation, requiring further research, particularly into populations with predispositions to type 1/type 17 inflammation.