AUTHOR=Shahid Muhammad , Cavalcante Paloma Araujo , Knight Cameron G. , Barkema Herman W. , Han Bo , Gao Jian , Cobo Eduardo R. 

TITLE=Murine and Human Cathelicidins Contribute Differently to Hallmarks of Mastitis Induced by Pathogenic Prototheca bovis Algae

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.00031

DOI=10.3389/fcimb.2020.00031

ISSN=2235-2988

ABSTRACT=<p><italic>Prototheca bovis</italic> (formerly <italic>P. zopfii</italic> genotype-II) is an opportunistic, achlorophyllous alga that causes mastitis in cows and skin disease in cats and dogs, as well as cutaneous lesions in both immunocompetent and immunosuppressed humans. Antifungal medications are commonly ineffective. This study aimed to investigate innate immune responses contributed by cathelicidins to <italic>P. bovis</italic> in the mammary gland using a mastitis model in mice deficient in the sole murine cathelicidin (<italic>Camp</italic>). We determined <italic>P. bovis</italic> caused acute mastitis in mice and induced <italic>Camp</italic> gene transcription. Whereas, <italic>Camp</italic><sup>−/−</sup> and <italic>Camp</italic><sup>+/+</sup> littermates had similar local algae burden, <italic>Camp</italic><sup>+/+</sup> mice produced more pro-inflammatory cytokines, TNF-α, and Cxcl-1. Likewise, <italic>Camp</italic><sup>+/+</sup> bone marrow-derived macrophages were more responsive to <italic>P. bovis</italic>, producing more <italic>TNF-</italic>α and <italic>Cxcl-1</italic>. Human cathelicidin (LL-37) exhibited a different effect against <italic>P. bovis</italic>; it had direct algicidal activity against <italic>P. bovis</italic> and lowered <italic>TNF-</italic>α, Cxcl-1, and <italic>IL-1</italic>β production in both cultured murine macrophages and mammary epithelial cells exposed to the pathogenic algae. In conclusion, cathelicidins were involved in protothecosis pathogenesis, with unique roles among the diverse peptide family. Whereas, endogenous cathelicidin (<italic>Camp</italic>) was key in mammary gland innate defense against <italic>P. bovis</italic>, human LL-37 had algicidal and immunomodulatory functions.</p>