Author:
V Harpf1,2*, L Riepl1, G Rambach1,2, V Fleischer1,2, C Lass-Flörl1,2, R Würzner1, C Speth1, 2
Author address:
1Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria
2Christian Doppler Laboratory for Invasive Fungal Infections, Innsbruck, Austria
Full conference title:
10th Advances Against Aspergillosis and Mucormycosis
Date: 2 February 2022
Abstract:
Purpose:
To enlighten the responsibility of the complement system, a part of the innate immunity, in the defense against mucormycosis, the purpose of our studies were, on the one hand, to compare the role of different parts of the complement system in a murine model of disseminated mucormycosis for different species and on the other hand, to study the relevance of the complement system for pathogenesis.
Methods:
Mice with a deficiency in complement C3 (DC3) or C6 (DC6) were intravenously infected with Lichtheimia corymbifera (LC), Lichtheimia ramosa (LR), Rhizopus arrhizus (RO), Rhizopus microsporus (RM), Rhizomucor pusillus (RmP) or Mucor circinelloides (M). Survival, clinical status, and immunological parameters were monitored over 14 days and compared to that of immunocompetent or neutropenic mice. Additionally, serum from healthy immunocompetent mice was analyzed for capacity to opsonize the fungi.
Results:
When intravenously infected with M or RO, there is no difference between DC3, DC6, neutropenic, and immunocompetent mice. Complement deficiencies represent a risk factor for a lethal outcome in LC, LR, RM, and RmP. LC and RM lead to higher mortality in complement deficient mice, compared to neutropenic animals. There is no significant difference between the lethality of DC3 and DC6 mice in intravenous infections with LC, M, RO, and RM. DC3 mice exhibited higher mortality than DC6 mice when infected with LR, whereas the opposite was the case in RmP infections. While the opsonization of LC, LR, RO, RM, and M spores inversely correlate to the virulence of these species in immunocompetent mice, showing low complement deposition on RM and RO spores, moderate deposition on LC and high deposition on M and LR, this correlation cannot be shown for RmP, which shows low mortality in the murine model and low opsonization in vitro.
Conclusion:
Complement plays an important role in the murine model of disseminated mucormycosis. Mortality of the complement-deficient animals varies between the species. Further investigations have to be performed to fully understand the immunopathogenesis of mucormycosis and help to fight the high morbidity and mortality of this disease.
Abstract Number: 76
Conference Year: 2022
Link to conference website: https://aaam2022.org/
URL Conference abstract: