Abstract
Prototheca bovis (formerly P. zopfii 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 P. bovis in the mammary gland using a mastitis model in mice deficient in the sole murine cathelicidin (Camp). We determined P. bovis caused acute mastitis in mice and induced Camp gene transcription. Whereas, Camp−/− and Camp+/+ littermates had similar local algae burden, Camp+/+ mice produced more pro-inflammatory cytokines, TNF-α, and Cxcl-1. Likewise, Camp+/+ bone marrow-derived macrophages were more responsive to P. bovis, producing more TNF-α and Cxcl-1. Human cathelicidin (LL-37) exhibited a different effect against P. bovis; it had direct algicidal activity against P. bovis and lowered TNF-α, Cxcl-1, and IL-1β 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 (Camp) was key in mammary gland innate defense against P. bovis, human LL-37 had algicidal and immunomodulatory functions.
Highlights
Prototheca species are unicellular achlorophyllous algae, 3–30 μm in diameter, that lack a specific glucosamine cell wall or chloroplasts (Baudelet et al, 2017)
Effects of endogenous cathelicidins in mastitis were studied in lactating Camp+/+ and Camp−/− mice intramammary infected with P. bovis isolated from a bovine clinical mastitis case
We used a Prototheca spp. identified as P. bovis following a taxonomic approach commonly accepted for Prototheca (Roesler et al, 2006) and a cytb-based genotyping used for unambiguous Prototheca spp. identification (Jagielski et al, 2018) based on the protothecal phylogeny (Jagielski et al, 2019a)
Summary
Prototheca species are unicellular achlorophyllous algae, 3–30 μm in diameter, that lack a specific glucosamine cell wall or chloroplasts (Baudelet et al, 2017). Their reproduction is asexual, with endospores being released from sporangia (Jagielski and Lagneau, 2007). Prototheca spp. are pathogenic and provoke a variety of maladies in animals. Infection with Prototheca spp. causes either cutaneous lesions or systemic. Prototheca spp. causes rare chronic skin or articular infections (Seok et al, 2013) or disseminated infections mostly in immunodeficient patients (Tello-Zavala et al, 2013)
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