Robust phagocyte recruitment controls the opportunistic fungal pathogen Mucor circinelloides in innate granulomas in vivo

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Robust phagocyte recruitment controls the opportunistic fungal pathogen Mucor circinelloides in innate granulomas in vivo. / Inglesfield, Sarah; Jasiulewicz, Aleksandra; Hopwood, Matthew; Tyrrell, James; Youlden, George; Mazon-Moya, Maria; Millington, Owain R.; Mostowy, Serge; Jabbari, Sara; Voelz, Kerstin.

In: mBio, Vol. 9, No. 2, 27.03.2018, p. e02010-17.

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@article{c2cada01e4e049329558dea73e270a5c,
title = "Robust phagocyte recruitment controls the opportunistic fungal pathogen Mucor circinelloides in innate granulomas in vivo",
abstract = "Mucormycosis is an emerging fungal infection with extremely high mortality rates in patients with defects in their innate immune response, specifically in functions mediated through phagocytes. However, we currently have a limited understanding of the molecular and cellular interactions between these innate immune effectors and mucormycete spores during the early immune response. Here, the early events of innate immune recruitment in response to infection by Mucor circinelloides spores are modelled by a combined in silico modelling approach and real-time in vivo microscopy. Phagocytes are rapidly recruited to the site of infection in a zebrafish larval model of mucormycosis. This robust early recruitment protects from disease onset in vivo. In silico analysis identified that protection is dependent on the number of phagocytes at the infection site, but not the speed of recruitment. The mathematical model highlights the role of proinflammatory signals for phagocyte recruitment, and the importance of inhibition of spore germination for protection from active fungal disease. These in silico data are supported by an in vivo lack of fungal spore killing and lack of reactive oxygen burst, which together result in latent fungal infection. During this latent stage of infection, spores are controlled in innate granulomas in vivo. Disease can be reactivated by immunosuppression. Together, these data represent the first in vivo real-time analysis of innate granuloma formation during the early stages of a fungal infection. The results highlight a potential latent stage during mucormycosis that should urgently be considered for clinical management of patients.",
author = "Sarah Inglesfield and Aleksandra Jasiulewicz and Matthew Hopwood and James Tyrrell and George Youlden and Maria Mazon-Moya and Millington, {Owain R.} and Serge Mostowy and Sara Jabbari and Kerstin Voelz",
year = "2018",
month = mar,
day = "27",
doi = "10.1128/mBio.02010-17.",
language = "English",
volume = "9",
pages = "e02010--17",
journal = "mBio",
issn = "2150-7511",
publisher = "American Society for Microbiology",
number = "2",

}

RIS

TY - JOUR

T1 - Robust phagocyte recruitment controls the opportunistic fungal pathogen Mucor circinelloides in innate granulomas in vivo

AU - Inglesfield, Sarah

AU - Jasiulewicz, Aleksandra

AU - Hopwood, Matthew

AU - Tyrrell, James

AU - Youlden, George

AU - Mazon-Moya, Maria

AU - Millington, Owain R.

AU - Mostowy, Serge

AU - Jabbari, Sara

AU - Voelz, Kerstin

PY - 2018/3/27

Y1 - 2018/3/27

N2 - Mucormycosis is an emerging fungal infection with extremely high mortality rates in patients with defects in their innate immune response, specifically in functions mediated through phagocytes. However, we currently have a limited understanding of the molecular and cellular interactions between these innate immune effectors and mucormycete spores during the early immune response. Here, the early events of innate immune recruitment in response to infection by Mucor circinelloides spores are modelled by a combined in silico modelling approach and real-time in vivo microscopy. Phagocytes are rapidly recruited to the site of infection in a zebrafish larval model of mucormycosis. This robust early recruitment protects from disease onset in vivo. In silico analysis identified that protection is dependent on the number of phagocytes at the infection site, but not the speed of recruitment. The mathematical model highlights the role of proinflammatory signals for phagocyte recruitment, and the importance of inhibition of spore germination for protection from active fungal disease. These in silico data are supported by an in vivo lack of fungal spore killing and lack of reactive oxygen burst, which together result in latent fungal infection. During this latent stage of infection, spores are controlled in innate granulomas in vivo. Disease can be reactivated by immunosuppression. Together, these data represent the first in vivo real-time analysis of innate granuloma formation during the early stages of a fungal infection. The results highlight a potential latent stage during mucormycosis that should urgently be considered for clinical management of patients.

AB - Mucormycosis is an emerging fungal infection with extremely high mortality rates in patients with defects in their innate immune response, specifically in functions mediated through phagocytes. However, we currently have a limited understanding of the molecular and cellular interactions between these innate immune effectors and mucormycete spores during the early immune response. Here, the early events of innate immune recruitment in response to infection by Mucor circinelloides spores are modelled by a combined in silico modelling approach and real-time in vivo microscopy. Phagocytes are rapidly recruited to the site of infection in a zebrafish larval model of mucormycosis. This robust early recruitment protects from disease onset in vivo. In silico analysis identified that protection is dependent on the number of phagocytes at the infection site, but not the speed of recruitment. The mathematical model highlights the role of proinflammatory signals for phagocyte recruitment, and the importance of inhibition of spore germination for protection from active fungal disease. These in silico data are supported by an in vivo lack of fungal spore killing and lack of reactive oxygen burst, which together result in latent fungal infection. During this latent stage of infection, spores are controlled in innate granulomas in vivo. Disease can be reactivated by immunosuppression. Together, these data represent the first in vivo real-time analysis of innate granuloma formation during the early stages of a fungal infection. The results highlight a potential latent stage during mucormycosis that should urgently be considered for clinical management of patients.

U2 - 10.1128/mBio.02010-17.

DO - 10.1128/mBio.02010-17.

M3 - Article

VL - 9

SP - e02010-17

JO - mBio

JF - mBio

SN - 2150-7511

IS - 2

ER -