Antibodies to a cell surface histone-like protein protect against Histoplasma capsulatum

Joshua D. Nosanchuk, Judith N. Steenbergen, Li Shi, George S. Deepe, Arturo Casadevall

Research output: Contribution to journalArticle

Abstract

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-7-γ 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.

Original languageEnglish (US)
Pages (from-to)1164-1175
Number of pages12
JournalJournal of Clinical Investigation
Volume112
Issue number8
DOIs
StatePublished - Oct 2003
Externally publishedYes

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Histoplasma
Histones
Antibodies
Proteins
Yeasts
Antigens
Fungi
Histoplasmosis
Mycoses
Phagocytosis
Interleukin-4
Interleukin-6
Pneumonia
Membrane Proteins
Vaccines
Eating
Macrophages
Lung
Growth
Infection

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Antibodies to a cell surface histone-like protein protect against Histoplasma capsulatum. / Nosanchuk, Joshua D.; Steenbergen, Judith N.; Shi, Li; Deepe, George S.; Casadevall, Arturo.

In: Journal of Clinical Investigation, Vol. 112, No. 8, 10.2003, p. 1164-1175.

Research output: Contribution to journalArticle

Nosanchuk, Joshua D. ; Steenbergen, Judith N. ; Shi, Li ; Deepe, George S. ; Casadevall, Arturo. / Antibodies to a cell surface histone-like protein protect against Histoplasma capsulatum. In: Journal of Clinical Investigation. 2003 ; Vol. 112, No. 8. pp. 1164-1175.
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