Complement, but Not Platelets, Plays a Pivotal Role in the Outcome of Mucormycosis In Vivo.

Autor: Harpf V; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria.; Christian Doppler Laboratory for Invasive Fungal Infections, 6020 Innsbruck, Austria., Rambach G; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria.; Christian Doppler Laboratory for Invasive Fungal Infections, 6020 Innsbruck, Austria., Parth N; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria.; Christian Doppler Laboratory for Invasive Fungal Infections, 6020 Innsbruck, Austria., Neurauter M; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria.; Christian Doppler Laboratory for Invasive Fungal Infections, 6020 Innsbruck, Austria., Fleischer V; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria.; Christian Doppler Laboratory for Invasive Fungal Infections, 6020 Innsbruck, Austria., Lackner M; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria., Lass-Flörl C; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria., Würzner R; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria., Speth C; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria.; Christian Doppler Laboratory for Invasive Fungal Infections, 6020 Innsbruck, Austria.
Jazyk: angličtina
Zdroj: Journal of fungi (Basel, Switzerland) [J Fungi (Basel)] 2023 Jan 25; Vol. 9 (2). Date of Electronic Publication: 2023 Jan 25.
DOI: 10.3390/jof9020162
Abstrakt: Background: Mucormycetes, a heterogeneous group of fungi, induce a life-threatening disease called mucormycosis. Immune deficiencies represent a major risk factor; hence, we wanted to illuminate the role of complement and platelets in the defense against mucormycetes.
Methods: Rhizopus arrhizus ( Ra ), Rhizopus microsporus ( Rm ), Lichtheimia ramosa ( Lr ), Lichtheimia corymbifera ( Lc ), Rhizomucor pusillus ( Rmp ), and Mucor circinelloides ( Mc ) spores were opsonized with human and mouse serum, and C1q, C3c, and terminal complement complex (C5b-9) deposition was measured. Additionally, thrombocytopenic, C3-deficient, or C6-deficient mice were intravenously infected with selected isolates. Survival and immunological parameters were monitored, and fungal burden was determined and compared to that of immunocompetent and neutropenic mice.
Results: In vitro experiments showed significant differences in complement deposition between mucormycetes. Mc isolates bound up to threefold more human C5b-9 than other mucormycetes. Lr , Lc , and Mc bound high levels of murine C3c, whereas human C3c deposition was reduced on Mc compared to Lr and Lc . Murine C3c deposition negatively correlated with virulence. Complement deficiencies and neutropenia, but not thrombocytopenia, were shown to be a risk factor for a lethal outcome.
Conclusion: Complement deposition varies between mucormycetes. Additionally, we demonstrated that complement and neutrophilic granulocytes, but not platelets, play an important role in a murine model of disseminated mucormycosis.
Databáze: MEDLINE
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