Immunomodulation for the Treatment of Fungal Infections: Opportunities and Challenges

Overview

Journal Front Cell Infect Microbiol

Specialties Cell Biology
Infectious Diseases
Microbiology

Date 2020 Oct 12

PMID 33042859

Citations 12

Authors

Muluneh Ademe

Affiliations

Soon will be listed here.

Abstract

Opportunistic fungal infections are major causes of morbidity and mortality in patients with single or multiple defects in their immunity. Antifungal agents targeting the pathogen remain the treatment of choice for fungal infections. However, antifungal agents are toxic to the host mainly due to the close evolutionary similarity of fungi and humans. Moreover, antifungal therapy is ineffective in patients with immunosuppression. For this reason, there is an increased demand to develop novel strategies to enhance immune function and augment the existing antifungal drugs. In recent times, targeting the immune system to improve impaired host immune responses becomes a reasonable approach to improve the effectiveness of antifungal drugs. In this regard, immunomodulating therapeutic agents that turn up the immune response in the fight against fungal infections hold promise for enhancing the efficacy and safety of conventional antifungal therapy. In general, immunomodulating therapies are safe with decreased risk of resistance and broad spectrum of activity. In this review, therefore, clinical evidences supporting the opportunities and challenges of immunomodulation therapies in the treatment of invasive fungal infections are included.

Citing Articles

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References

Nikolajeva O, Mijovic A, Hess D, Tatam E, Amrolia P, Chiesa R . Single-donor granulocyte transfusions for improving the outcome of high-risk pediatric patients with known bacterial and fungal infections undergoing stem cell transplantation: a 10-year single-center experience. Bone Marrow Transplant. 2015; 50(6):846-9. DOI: 10.1038/bmt.2015.53. View

Casadevall A, Pirofski L . Immunoglobulins in defense, pathogenesis, and therapy of fungal diseases. Cell Host Microbe. 2012; 11(5):447-56. PMC: 3360875. DOI: 10.1016/j.chom.2012.04.004. View

Wright C, Ward A, Russell A . Granulocyte Colony-Stimulating Factor and Its Potential Application for Skeletal Muscle Repair and Regeneration. Mediators Inflamm. 2018; 2017:7517350. PMC: 5738577. DOI: 10.1155/2017/7517350. View

Davies J, Stringaris K, Barrett A, Rezvani K . Opportunities and limitations of natural killer cells as adoptive therapy for malignant disease. Cytotherapy. 2014; 16(11):1453-1466. PMC: 4190023. DOI: 10.1016/j.jcyt.2014.03.009. View

Giles F . Monocyte-macrophages, granulocyte-macrophage colony-stimulating factor, and prolonged survival among patients with acute myeloid leukemia and stem cell transplants. Clin Infect Dis. 1998; 26(6):1282-9. DOI: 10.1086/516361. View

Boniche C, Rossi S, Kischkel B, Barbalho F, Moura A, Nosanchuk J . Immunotherapy against Systemic Fungal Infections Based on Monoclonal Antibodies. J Fungi (Basel). 2020; 6(1). PMC: 7151209. DOI: 10.3390/jof6010031. View

Brudno J, Kochenderfer J . Toxicities of chimeric antigen receptor T cells: recognition and management. Blood. 2016; 127(26):3321-30. PMC: 4929924. DOI: 10.1182/blood-2016-04-703751. View

Stevens D, Brummer E, Clemons K . Interferon- gamma as an antifungal. J Infect Dis. 2006; 194 Suppl 1:S33-7. DOI: 10.1086/505357. View

Graybill J, Bocanegra R, Najvar L, Loebenberg D, Luther M . Granulocyte colony-stimulating factor and azole antifungal therapy in murine aspergillosis: role of immune suppression. Antimicrob Agents Chemother. 1998; 42(10):2467-73. PMC: 105859. DOI: 10.1128/AAC.42.10.2467. View

10.

Rudkin F, Raziunaite I, Workman H, Essono S, Belmonte R, MacCallum D . Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis. Nat Commun. 2018; 9(1):5288. PMC: 6290022. DOI: 10.1038/s41467-018-07738-1. View

11.

Roy R, Klein B . Dendritic cells in antifungal immunity and vaccine design. Cell Host Microbe. 2012; 11(5):436-46. PMC: 3401965. DOI: 10.1016/j.chom.2012.04.005. View

12.

Tsai M, Thauland T, Huang A, Bun C, Fitzwater S, Krogstad P . Disseminated Coccidioidomycosis Treated with Interferon-γ and Dupilumab. N Engl J Med. 2020; 382(24):2337-2343. PMC: 7333509. DOI: 10.1056/NEJMoa2000024. View

13.

Papadopoulou A, Kaloyannidis P, Yannaki E, Cruz C . Adoptive transfer of Aspergillus-specific T cells as a novel anti-fungal therapy for hematopoietic stem cell transplant recipients: Progress and challenges. Crit Rev Oncol Hematol. 2015; 98:62-72. DOI: 10.1016/j.critrevonc.2015.10.005. View

14.

Stuehler C, Kuenzli E, Jaeger V, Baettig V, Ferracin F, Rajacic Z . Immune Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation and Association With Occurrence and Outcome of Invasive Aspergillosis. J Infect Dis. 2015; 212(6):959-67. DOI: 10.1093/infdis/jiv143. View

15.

Marr K, Carter R, Crippa F, Wald A, Corey L . Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002; 34(7):909-17. DOI: 10.1086/339202. View

16.

Vanitha S, Chaubey N, Ghosh S, Sanpui P . Recombinant human granulocyte macrophage colony stimulating factor (hGM-CSF): Possibility of nanoparticle-mediated delivery in cancer immunotherapy. Bioengineered. 2016; 8(2):120-123. PMC: 5398574. DOI: 10.1080/21655979.2016.1212136. View

17.

Shiomi A, Usui T . Pivotal roles of GM-CSF in autoimmunity and inflammation. Mediators Inflamm. 2015; 2015:568543. PMC: 4370199. DOI: 10.1155/2015/568543. View

18.

Depil S, Duchateau P, Grupp S, Mufti G, Poirot L . 'Off-the-shelf' allogeneic CAR T cells: development and challenges. Nat Rev Drug Discov. 2020; 19(3):185-199. DOI: 10.1038/s41573-019-0051-2. View

19.

Tramsen L, Schmidt S, Roeger F, Schubert R, Salzmann-Manrique E, Latge J . Immunosuppressive compounds exhibit particular effects on functional properties of human anti-Aspergillus Th1 cells. Infect Immun. 2014; 82(6):2649-56. PMC: 4019178. DOI: 10.1128/IAI.01700-14. View

20.

Rowe J . Concurrent use of growth factors and chemotherapy in acute leukemia. Curr Opin Hematol. 2000; 7(3):197-202. DOI: 10.1097/00062752-200005000-00012. View