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

Joshua D Breidenbach; Benjamin W. French; Lauren M. Stanoszek; John-paul Lavik; Krishna Rao Maddipati; Sanduni H. Premathilaka; David Baliu-Rodriguez; Bivek Timalsina; Vaishnavi Aradhyula; Shivani Patel; Apruva C. Lad; Irum Syed; Andrew Kleinhenz; Thomas M. Blomquist; Amira F. Gohara; Prabhatchandra Dube; Shungang Zhang; Dhilhani Faleel; Fatimah K. Khalaf; Dragan Isailovic; R. Mark Wooten; James Willey; Jeffrey Hammersley; Nikolai N. Modyanov; Deepak Malhotra; Lance D Dworkin; David J. Kennedy; Steven T. Haller

doi:10.20944/preprints202410.0463.v1

Preprint Article Version 1 This version is not peer-reviewed

Version 1 : Received: 24 September 2024 / Approved: 7 October 2024 / Online: 7 October 2024 (11:28:27 CEST)

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 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.

Microcystin; MC-LR; aerosol; harmful algal bloom; inflammation

Biology and Life Sciences, Toxicology

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

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