title: Central importance of immunoglobulin A in host defense against Giardia spp.
abstract: The protozoan pathogen Giardia is an important cause of parasitic diarrheal disease worldwide. It colonizes the lumen of the small intestine, suggesting that effective host defenses must act luminally. Immunoglobulin A (IgA) antibodies are presumed to be important for controlling Giardia infection, but direct evidence for this function is lacking. B-cell-independent effector mechanisms also exist and may be equally important for antigiardial host defense. To determine the importance of the immunoglobulin isotypes that are transported into the intestinal lumen, IgA and IgM, for antigiardial host defense, we infected gene-targeted mice lacking IgA-expressing B-cells, IgM-secreting B-cells, or all B-cells as controls with Giardia muris or Giardia lamblia GS/M-83-H7. We found that IgA-deficient mice could not eradicate either G. muris or G. lamblia infection, demonstrating that IgA is required for their clearance. Furthermore, although neither B-cell-deficient nor IgA-deficient mice could clear G. muris infections, IgA-deficient mice controlled infection significantly better than B-cell-deficient mice, suggesting the existence of B-cell-dependent but IgA-independent antigiardial defenses. In contrast, mice deficient for secreted IgM antibodies cleared G. muris infection normally, indicating that they have no unique functions in antigiardial host defense. These data, together with the finding that B-cell-deficient mice have some, albeit limited, residual capacity to control G. muris infection, show that IgA-dependent host defenses are central for eradicating Giardia spp. Moreover, B-cell-dependent but IgA-independent and B-cell-independent antigiardial host defenses exist but are less important for controlling infection.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California 92093-0623, USA.
authors.forename: T Dianne
authors.initials: TD
authors.lastname: Langford
authors.forename: Michael P
authors.initials: MP
authors.lastname: Housley
authors.forename: Marianne
authors.initials: M
authors.lastname: Boes
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Chen
authors.forename: Martin F
authors.initials: MF
authors.lastname: Kagnoff
authors.forename: Frances D
authors.initials: FD
authors.lastname: Gillin
authors.forename: Lars
authors.initials: L
authors.lastname: Eckmann
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005872:Giardia / Q000276:immunology; D016829:Giardia lamblia; D005873:Giardiasis / Q000276:immunology* / Q000517:prevention & control; D007110:Immunity, Active / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D000913:Antibodies, Protozoan; D007070:Immunoglobulin A; D007075:Immunoglobulin M