Antibodies to a cell surface histone-like protein protect against Histoplasma capsulatum.
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.
Nosanchuk
Joshua D
JD
Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, New York, New York 10461, USA. nosanchu@aecom.yu.edu
Steenbergen
Judith N
JN
Shi
Li
L
Deepe
George S
GS
Casadevall
Arturo
A
D000595:Amino Acid Sequence; D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000946:Antigens, Fungal / Q000032:analysis; D001483:Base Sequence; D005260:Female; D005656:Fungal Proteins / Q000276:immunology*; D006657:Histones / Q000276:immunology*; D006658:Histoplasma / Q000276:immunology*; D006660:Histoplasmosis / Q000517:prevention & control*; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010587:Phagocytosis
D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D000946:Antigens, Fungal; D005656:Fungal Proteins; D006657:Histones; D015847:Interleukin-4; D007371:Interferon-gamma