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Fungal dissemination is limited by liver macrophage filtration of the blood

Author

Listed:
  • Donglei Sun

    (University of Maryland)

  • Peng Sun

    (University of Maryland)

  • Hongmei Li

    (University of Maryland
    South China Agricultural University)

  • Mingshun Zhang

    (University of Maryland
    Nanjing Medical University)

  • Gongguan Liu

    (University of Maryland)

  • Ashley B. Strickland

    (University of Maryland)

  • Yanli Chen

    (University of Maryland)

  • Yong Fu

    (University of Maryland)

  • Juan Xu

    (University of Maryland
    Nanjing Medical University)

  • Mohammed Yosri

    (University of Maryland
    Al-Azhar University)

  • Yuchen Nan

    (Northwest A&F University)

  • Hong Zhou

    (Nanjing Medical University)

  • Xiquan Zhang

    (South China Agricultural University)

  • Meiqing Shi

    (University of Maryland)

Abstract

Fungal dissemination into the bloodstream is a critical step leading to invasive fungal infections. Here, using intravital imaging, we show that Kupffer cells (KCs) in the liver have a prominent function in the capture of circulating Cryptococcus neoformans and Candida albicans, thereby reducing fungal dissemination to target organs. Complement C3 but not C5, and complement receptor CRIg but not CR3, are involved in capture of C. neoformans. Internalization of C. neoformans by KCs is subsequently mediated by multiple receptors, including CR3, CRIg, and scavenger receptors, which work synergistically along with C5aR signaling. Following phagocytosis, the growth of C. neoformans is inhibited by KCs in an IFN-γ independent manner. Thus, the liver filters disseminating fungi from circulation via KCs, providing a mechanistic explanation for the enhanced risk of cryptococcosis among individuals with liver diseases, and suggesting a therapeutic strategy to prevent fungal dissemination through enhancing KC functions.

Suggested Citation

  • Donglei Sun & Peng Sun & Hongmei Li & Mingshun Zhang & Gongguan Liu & Ashley B. Strickland & Yanli Chen & Yong Fu & Juan Xu & Mohammed Yosri & Yuchen Nan & Hong Zhou & Xiquan Zhang & Meiqing Shi, 2019. "Fungal dissemination is limited by liver macrophage filtration of the blood," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12381-5
    DOI: 10.1038/s41467-019-12381-5
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