The study shows that the human peptide LL‑37 can directly kill the algae Prototheca bovis, which causes infections in cows and sometimes in humans, and it also calms down inflammation in mouse immune cells. In mice, their own cathelicidin (Camp) makes inflammation worse but doesn’t kill the algae.

<i>Prototheca bovis</i> (formerly <i>P. zopfii</i> 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 <i>P. bovis</i> in the mammary gland using a mastitis model in mice deficient in the sole murine cathelicidin (<i>Camp</i>). We determined <i>P. bovis</i> caused acute mastitis in mice and induced <i>Camp</i> gene transcription. Whereas, <i>Camp</i>^-/- and <i>Camp</i>^+/+ littermates had similar local algae burden, <i>Camp</i>^+/+ mice produced more pro-inflammatory cytokines, TNF-&#x3b1;, and Cxcl-1. Likewise, <i>Camp</i>^+/+ bone marrow-derived macrophages were more responsive to <i>P. bovis</i>, producing more <i>TNF-</i>&#x3b1; and <i>Cxcl-1</i>. Human cathelicidin (LL-37) exhibited a different effect against <i>P. bovis</i>; it had direct algicidal activity against <i>P. bovis</i> and lowered <i>TNF-</i>&#x3b1;, Cxcl-1, and <i>IL-1</i>&#x3b2; 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 (<i>Camp</i>) was key in mammary gland innate defense against <i>P. bovis</i>, human LL-37 had algicidal and immunomodulatory functions.