HOST IMMUNE RESPONSE TO FUNGAL SEPSIS: NEUTROPHIL EXTRACELLULAR TRAPS AND CIRCULATING IMMUNE COMPLEX FORMATION
DOI: http://dx.doi.org/10.30970/sbi.1904.855
Abstract
Background. Sepsis is a major global health problem, with fungal pathogens such as Candida albicans emerging as a significant cause of invasive infection. Fungal sepsis has a higher mortality rate than bacterial sepsis and is complicated by antifungal resistance. Although neutrophil extracellular traps (NETs) help to contain fungi, excessive NETs can contribute to inflammation and tissue injury. Understanding these mechanisms could reveal markers of disease activity and new therapeutic targets.
Materials and Methods. Fungal sepsis was induced in twelve male BALB/c mice via an intraperitoneal injection of Meyerozyma guilliermondii (107 cells per mouse). Blood was collected at the beginning of the study and then on days 1–3, 7–9, and 13–15. Serum was analyzed for IgG, IgM, circulating immune complexes (ELISA), and extracellular DNA (fluorescence assay).
Results and Discussion. In mice with fungal sepsis, IgG levels remained stable while IgM levels increased significantly between days 7 and 9, before declining from day 13. IgG–IgM immune complexes peaked around days 8–9, reflecting active antigen-antibody responses. Free DNA levels, which indicate NETs formation, increased by day 7 and then declined, showing early neutrophil activation followed by humoral control. Together, these findings suggest a coordinated immune response in which NETs and immune complexes contribute to both pathogen control and inflammation.
Conclusion. Fungal sepsis induced by Meyerozyma guilliermondii resulted in early NETosis and an increase in IgM and immune complexes. IgM levels peaked on days 7–9 before declining. Unlike Candida albicans, this strain does not cause rapid lethality, enabling detailed tracking of disease progression over time. After day 9, immune parameters began to normalize, indicating the resolution of the acute phase and supporting the usefulness of this model for studying host immune dynamics in fungal sepsis.
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| Alflen, A., Aranda Lopez, P., Hartmann, A.-K., Maxeiner, J., Bosmann, M., Sharma, A., Platten, J., Ries, F., Beckert, H., Ruf, W., & Radsak, M. P. (2020). Neutrophil extracellular traps impair fungal clearance in a mouse model of invasive pulmonary aspergillosis. Immunobiology, 225(1), 151867. doi:10.1016/j.imbio.2019.11.002 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Block, H., & Zarbock, A. (2021). A fragile balance: does neutrophil extracellular trap formation drive pulmonary disease progression? Cells, 10(8), 1932. doi:10.3390/cells10081932 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D. S., Weinrauch, Y., & Zychlinsky, A. (2004). Neutrophil extracellular traps kill bacteria. Science, 303(5663), 1532-1535. doi:10.1126/science.1092385 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Delgado-Rizo, V., Martínez-Guzmán, M. A., Iñiguez-Gutierrez, L., García-Orozco, A., Alvarado-Navarro, A., & Fafutis-Morris, M. (2017). Neutrophil extracellular traps and its implications in inflammation: an overview. Frontiers in Immunology, 8, 81. doi:10.3389/fimmu.2017.00081 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Desai, J. V, & Lionakis, M. S. (2018). The role of neutrophils in host defense against invasive fungal infections. Current Clinical Microbiology Reports, 5(3), 181-189. doi:10.1007/s40588-018-0098-6 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Dumych, T., Paryzhak, S., & Bilyy, R. (2019). Involvement of neutrophil hydrolytic enzymes in the modification of circulating immune complexes under the circumstaces of experimental sepsis. Proceedings of the Shevchenko Scientific Society. Medical Sciences, 55(1), 31-39. doi:10.25040/ntsh2019.01.03 Crossref ● Google Scholar | ||||
| ||||
| Guarino, M., Perna, B., Cesaro, A. E., Maritati, M., Spampinato, M. D., Contini, C., & De Giorgio, R. (2023). 2023 update on sepsis and septic shock in adult patients: management in the emergency department. Journal of Clinical Medicine, 12(9), 3188. doi:10.3390/jcm12093188 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Kimball, A. S., Obi, A. T., Diaz, J. A., & Henke, P. K. (2016). The emerging role of NETs in venous thrombosis and immunothrombosis. Frontiers in Immunology, 7. doi:10.3389/fimmu.2016.00236 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Lass-Flörl, C., Kanj, S. S., Govender, N. P., Thompson, G. R., Ostrosky- Zeichner, L., & Govrins, M. A. (2024). Invasive candidiasis. Nature Reviews Disease Primers, 10(1), 20. doi.:10.1038/s41572-024-00503-3 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Lehman, H. K., & Segal, B. H. (2020). The role of neutrophils in host defense and disease. Journal of Allergy and Clinical Immunology, 145(6), 1535-1544. doi:10.1016/j.jaci.2020.02.038 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Liang, C., Lian, N., & Li, M. (2022). The emerging role of neutrophil extracellular traps in fungal infection. Frontiers in Cellular and Infection Microbiology, 12, 900895. doi:10.3389/fcimb.2022.900895 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Lopes, J. P., & Lionakis, M. S. (2022). Pathogenesis and virulence of Candida albicans. Virulence, 13(1), 89-121. doi:10.1080/21505594.2021.2019950 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Manika, M. M., Situakibanza, H. N.-T., Iteke, R. F., Mujing'a, F. M., Kakisingi, C. N., Matanda, S. K., Teta, I. M., Mukalay, Y. M., Tshibwaya, N. M., Ilunga, E. K., Kabamba, M. N., Barhayiga, B. N., Tano, A. K., & Kapend'a, L. K. (2025). Fungal sepsis in the ICU: etiology and susceptibility profile to antifungals in Lubumbashi, Democratic Republic of the Congo. doi:10.20944/preprints202503.0733.v1 Crossref ● Google Scholar | ||||
| ||||
| Parasuraman, S., Raveendran, R., & Kesavan, R. (2010). Blood sample collection in small laboratory animals. Journal of Pharmacology and Pharmacotherapeutics, 1(2), 87. doi:10.4103/0976-500X.72350 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Paryzhak, S., Dumych, T., Mahorivska, I., Boichuk, M., Bila, G., Peshkova, S., Nehrych, T., & Bilyy, R. (2018). Neutrophil-released enzymes can influence composition of circulating immune complexes in multiple sclerosis. Autoimmunity, 51(6), 297-303. doi:10.1080/08916934.2018.1514390 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Retter, A., Singer, M., & Annane, D. (2025). "The NET effect": neutrophil extracellular traps - a potential key component of the dysregulated host immune response in sepsis. Critical Care, 29(1), 59. doi:10.1186/s13054-025-05283-0 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Rosales, C. (2018). Neutrophil: a cell with many roles in inflammation or several cell types? Frontiers in Physiology, 9, 113. doi:10.3389/fphys.2018.00113 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Sathe, A., & Cusick, J. K. (2025). Biochemistry, immunoglobulin M. In: StatPearls. StatPearls Publishing. PubMed ● Google Scholar | ||||
| ||||
| Soriano, A., Honore, P. M., Puerta-Alcalde, P., Garcia-Vidal, C., Pagotto, A., Gonçalves-Bradley, D. C., & Verweij, P. E. (2023). Invasive candidiasis: current clinical challenges and unmet needs in adult populations. Journal of Antimicrobial Chemotherapy, 78(7), 1569-1585. doi:10.1093/jac/dkad139 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Yancey, K. B., & Lawley, T. J. (1984). Circulating immune complexes: their immunochemistry, biology, and detection in selected dermatologic and systemic diseases. Journal of the American Academy of Dermatology, 10(5), 711-731. doi:10.1016/S0190-9622(84)70087-9 Crossref ● PubMed ● Google Scholar | ||||
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