TY - JOUR
T1 - Protective effect of fungal extracellular vesicles against murine candidiasis
AU - Vargas, Gabriele
AU - Honorato, Leandro
AU - Guimarães, Allan Jefferson
AU - Rodrigues, Marcio L.
AU - Reis, Flavia C.G.
AU - Vale, André M.
AU - Ray, Anjana
AU - Nosanchuk, Joshua Daniel
AU - Nimrichter, Leonardo
N1 - Funding Information:
This work was supported by grants from the Brazilian agency Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, grants 405520/2018‐2, 440015/2018‐9, and 301304/2017‐3 to M.L.R.; 311179/2017‐7 and 408711/2017‐7 to L.N.), FAPERJ (E‐26/202.809/2018 to L.N and E‐26/202.696/2018 to A.J.G) and Fiocruz (grants VPPCB‐007‐FIO‐18 and VPPIS‐001‐FIO18) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Finance Code 001). JDN was supported in part by R21AI124797.
Funding Information:
Conselho Nacional de Desenvolvimento Científico e Tecnológico, Grant/Award Numbers: 301304/2017‐3, 311179/2017‐7, 405520/2018‐2, 408711/2017‐7, 440015/2018‐9; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Grant/Award Number: CAPES, Finance Code 001; Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Grant/Award Numbers: E‐26/202.809/2018, E‐26/202.696/2018; Fundação Oswaldo Cruz, Grant/Award Numbers: VPPCB‐007‐FIO‐18, VPPIS‐001‐FIO18; NIH, Grant/Award Number: R21AI124797 Funding information
Publisher Copyright:
© 2020 John Wiley & Sons Ltd
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Extracellular vesicles (EVs) are lipid bilayered compartments released by virtually all living cells, including fungi. Among the diverse molecules carried by fungal EVs, a number of immunogens, virulence factors and regulators have been characterised. Within EVs, these components could potentially impact disease outcomes by interacting with the host. From this perspective, we previously demonstrated that EVs from Candida albicans could be taken up by and activate macrophages and dendritic cells to produce cytokines and express costimulatory molecules. Moreover, pre-treatment of Galleria mellonella larvae with fungal EVs protected the insects against a subsequent lethal infection with C. albicans yeasts. These data indicate that C. albicans EVs are multi-antigenic compartments that activate the innate immune system and could be exploited as vaccine formulations. Here, we investigated whether immunisation with C. albicans EVs induces a protective effect against murine candidiasis in immunosuppressed mice. Total and fungal antigen-specific serum IgG antibodies increased by 21 days after immunisation, confirming the efficacy of the protocol. Vaccination decreased fungal burden in the liver, spleen and kidney of mice challenged with C. albicans. Splenic levels of cytokines indicated a lower inflammatory response in mice immunised with EVs when compared with EVs + Freund's adjuvant (ADJ). Higher levels of IL-12p70, TNFα and IFNγ were detected in mice vaccinated with EVs + ADJ, while IL-12p70, TGFβ, IL-4 and IL-10 were increased when no adjuvants were added. Full protection of lethally challenged mice was observed when EVs were administered, regardless the presence of adjuvant. Physical properties of the EVs were also investigated and EVs produced by C. albicans were relatively stable after storage at 4, −20 or −80°C, keeping their ability to activate dendritic cells and to protect G. mellonella against a lethal candidiasis. Our data suggest that fungal EVs could be a safe source of antigens to be exploited in vaccine formulations.
AB - Extracellular vesicles (EVs) are lipid bilayered compartments released by virtually all living cells, including fungi. Among the diverse molecules carried by fungal EVs, a number of immunogens, virulence factors and regulators have been characterised. Within EVs, these components could potentially impact disease outcomes by interacting with the host. From this perspective, we previously demonstrated that EVs from Candida albicans could be taken up by and activate macrophages and dendritic cells to produce cytokines and express costimulatory molecules. Moreover, pre-treatment of Galleria mellonella larvae with fungal EVs protected the insects against a subsequent lethal infection with C. albicans yeasts. These data indicate that C. albicans EVs are multi-antigenic compartments that activate the innate immune system and could be exploited as vaccine formulations. Here, we investigated whether immunisation with C. albicans EVs induces a protective effect against murine candidiasis in immunosuppressed mice. Total and fungal antigen-specific serum IgG antibodies increased by 21 days after immunisation, confirming the efficacy of the protocol. Vaccination decreased fungal burden in the liver, spleen and kidney of mice challenged with C. albicans. Splenic levels of cytokines indicated a lower inflammatory response in mice immunised with EVs when compared with EVs + Freund's adjuvant (ADJ). Higher levels of IL-12p70, TNFα and IFNγ were detected in mice vaccinated with EVs + ADJ, while IL-12p70, TGFβ, IL-4 and IL-10 were increased when no adjuvants were added. Full protection of lethally challenged mice was observed when EVs were administered, regardless the presence of adjuvant. Physical properties of the EVs were also investigated and EVs produced by C. albicans were relatively stable after storage at 4, −20 or −80°C, keeping their ability to activate dendritic cells and to protect G. mellonella against a lethal candidiasis. Our data suggest that fungal EVs could be a safe source of antigens to be exploited in vaccine formulations.
KW - Candida albicans
KW - extracellular vesicles
KW - fungal pathogenesis
KW - vaccines
UR - http://www.scopus.com/inward/record.url?scp=85088318341&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088318341&partnerID=8YFLogxK
U2 - 10.1111/cmi.13238
DO - 10.1111/cmi.13238
M3 - Article
C2 - 32558196
AN - SCOPUS:85088318341
SN - 1462-5814
VL - 22
JO - Cellular Microbiology
JF - Cellular Microbiology
IS - 10
M1 - e13238
ER -
