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Experimental Therapeutics

The Lymphocytic Scavenger Receptor CD5 Shows Therapeutic Potential in Mouse Models of Fungal Infection

María Velasco-de Andrés, Cristina Català, Sergi Casadó-Llombart, Mario Martínez-Florensa, Inês Simões, Joaquín García-Luna, Gustavo Mourglia-Ettlin, Óscar Zaragoza, Esther Carreras, Francisco Lozano
María Velasco-de Andrés
aImmunoreceptors of the Innate and Adaptive System, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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Cristina Català
aImmunoreceptors of the Innate and Adaptive System, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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Sergi Casadó-Llombart
aImmunoreceptors of the Innate and Adaptive System, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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Mario Martínez-Florensa
aImmunoreceptors of the Innate and Adaptive System, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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Inês Simões
aImmunoreceptors of the Innate and Adaptive System, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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Joaquín García-Luna
bÁrea Inmunología, Facultad de Química/Facultad de Ciencias, DEPBIO/IQB, Universidad de la República, Montevideo, Uruguay
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Gustavo Mourglia-Ettlin
bÁrea Inmunología, Facultad de Química/Facultad de Ciencias, DEPBIO/IQB, Universidad de la República, Montevideo, Uruguay
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Óscar Zaragoza
cMycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Spain
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Esther Carreras
aImmunoreceptors of the Innate and Adaptive System, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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Francisco Lozano
aImmunoreceptors of the Innate and Adaptive System, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
dServei d’Immunologia, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Barcelona, Spain
eDepartament de Biomedicina, Universitat de Barcelona, Barcelona, Spain
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  • ORCID record for Francisco Lozano
DOI: 10.1128/AAC.01103-20
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ABSTRACT

Invasive fungal diseases represent an unmet clinical need that could benefit from novel immunotherapeutic approaches. Host pattern recognition receptors (e.g., Toll-like receptors, C-type lectins, or scavenger receptors) that sense conserved fungal cell wall constituents may provide suitable immunotherapeutic antifungal agents. Thus, we explored the therapeutic potential of the lymphocyte class I scavenger receptor CD5, a nonredundant component of the antifungal host immune response that binds to fungal β-glucans. Antifungal properties of the soluble ectodomain of human CD5 (shCD5) were assessed in vivo in experimental models of systemic fungal infection induced by pathogenic species (Candida albicans and Cryptococcus neoformans). In vitro mechanistic studies were performed by means of fungus-spleen cell cocultures. shCD5-induced survival of lethally infected mice was dose and time dependent and concomitant with reduced fungal load and increased leukocyte infiltration in the primary target organ. Additive effects were observed in vivo after shCD5 was combined with suboptimal doses of fluconazole. Ex vivo addition of shCD5 to fungus-spleen cell cocultures increased the release of proinflammatory cytokines involved in antifungal defense (tumor necrosis factor alpha and gamma interferon) and reduced the number of viable C. albicans organisms. The results prompt further exploration of the adjunctive therapeutic potential of shCD5 in severe invasive fungal diseases.

FOOTNOTES

    • Received 29 May 2020.
    • Returned for modification 10 August 2020.
    • Accepted 6 October 2020.
    • Accepted manuscript posted online 12 October 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

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The Lymphocytic Scavenger Receptor CD5 Shows Therapeutic Potential in Mouse Models of Fungal Infection
María Velasco-de Andrés, Cristina Català, Sergi Casadó-Llombart, Mario Martínez-Florensa, Inês Simões, Joaquín García-Luna, Gustavo Mourglia-Ettlin, Óscar Zaragoza, Esther Carreras, Francisco Lozano
Antimicrobial Agents and Chemotherapy Dec 2020, 65 (1) e01103-20; DOI: 10.1128/AAC.01103-20

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The Lymphocytic Scavenger Receptor CD5 Shows Therapeutic Potential in Mouse Models of Fungal Infection
María Velasco-de Andrés, Cristina Català, Sergi Casadó-Llombart, Mario Martínez-Florensa, Inês Simões, Joaquín García-Luna, Gustavo Mourglia-Ettlin, Óscar Zaragoza, Esther Carreras, Francisco Lozano
Antimicrobial Agents and Chemotherapy Dec 2020, 65 (1) e01103-20; DOI: 10.1128/AAC.01103-20
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KEYWORDS

scavenger receptors
CD5
immunotherapy
β-glucan
fungal infection
Candida albicans
Cryptococcus neoformans
fluconazole
antifungal therapy

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