Antibodies to a cell surface histone-like protein protect against Histoplasma capsulatum
Open accessAbstract
A protective role for antibodies has not previously been described for host defense against the pathogenic fungus Histoplasma capsulatum (Hc). Mouse mAb's were generated from mice immunized with Hc yeast that binds the cell surface of Hc. Administration of mAb's before Hc infection reduced fungal burden, decreased pulmonary inflammation, and prolonged survival in a murine infection model. Protection mediated by mAb's was associated with enhanced levels of IL-4, IL-6, and IFN-gamma in the lungs of infected mice. The mAb's increased phagocytosis of yeast by J774.16 cells through a CR3-dependent process. Ingestion of mAb-opsonized Hc by J774.16 macrophage-like cells was associated with yeast cell growth inhibition and killing. The mAb's bound to a 17-kDa antigen expressed on the surface of Hc. The antigen was identified as a histone H2B-like protein. This study establishes that mAb's to a cell surface protein of Hc alter the intracellular fate of the fungus and mediate protection in a murine model of lethal histoplasmosis, and it suggests a new candidate antigen for vaccine development.
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It is possible to generate protective mAbs against many viruses and microorganisms.
“there is ample evidence that it is possible to generate protective mAbs against many viruses and microorganisms (Teitelbaum et al, 1998; Nosanchuk et al, 2003; Both et al, 2013).”
From mRNA mediates passive vaccination against infectious agents, toxins, and tumors (2017) · cites this paper as Nosanchuk et al, 2003
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References 64 · Cited by 178
- Authors
- Nosanchuk, J. D., Steenbergen, J. N., Shi, L., Deepe, G. S., & Casadevall, A.
- Affiliations
- Albert Einstein College of Medicine (US)
- Yeshiva University (US)
- University of Cincinnati (US)
- Corresponding author
- Shi, Li
- Venue
- Journal of Clinical Investigation
- Published
- 2003-10-15
- Volume
- 112
- Issue
- 8
- Pages
- 1164-1175
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC213494
- OpenAlex
- W1965606695
- Cited by
- 178
- References
- 64
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 11 · 2019: 8 · 2018: 8 · 2017: 13 · 2016: 6 · 2015: 7 · 2014: 8 · 2013: 7 · 2012: 11
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institutes of Health (5r01hl059842-23, 5r01ai052733-16, CA13330)
- Center for AIDS Research, University of Washington
- National Heart, Lung, and Blood Institute (HL 59842, R01-HL059842)
- National Cancer Institute (CA‐13330, P30CA013330)
- National Institute of General Medical Sciences (T32-GM-07491, T32GM007491)
- National Institute of Allergy and Infectious Diseases (AI52733, AI-34361, AI13342, R37AI042747, R01-AI052733, R01AI034361, AI42747, AI33774, R01AI033774)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK20541, P60DK020541, P30DK020541)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- Histoplasma capsulatum, histoplasmosis, monoclonal antibodies, antibody-mediated protection, opsonization, CR3, phagocytosis, macrophages, cytokines, vaccine candidate antigens, fungal infection
- MeSH terms
- Amino Acid Sequence, Animals, Antibodies, Fungal, Antibodies, Monoclonal, Antigens, Fungal, Base Sequence, Female, Fungal Proteins, Histones, Histoplasma, Histoplasmosis, Immunization, Passive, Interferon-gamma, Macrophages, Mice, Inbred BALB C, Mice, Inbred C57BL, Molecular Sequence Data, Phagocytosis, Interleukin-4, Mice
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