Parasitic and Fungal Triggers

Sterba, Gary; Sterba, Yonit

doi:10.1007/978-3-030-22094-5_20

Cited by 1 publication

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“…This fact might result from the early death of the animals with shorter fungal growth and, therefore, decreased fungal DNA in the organs. Hence, we can rule out fungal burden in the organs as the cause of reaching the humane endpoint, but rather it is a cytokine storm syndrome [ 51 ] and/or massive thrombosis due to the angioinvasion, which would fit with the highest platelet activation in immunocompetent animals ( Figure 6 ).…”

Section: Discussionmentioning

confidence: 99%

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

Harpf

Rambach

Parth

et al. 2023

JoF

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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.

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Section: Discussionmentioning

confidence: 99%