Central Importance of Immunoglobulin A in Host Defense againstGiardiaspp

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 IgAindependent and B-cell-independent antigiardial host defenses exist but are less important for controlling infection.

Household and personal factors are sources of heterogenity in intestinal parasite clearance among Mexican children 6–15 months of age supplemented with vitamin A and zinc

“…For A. lumbricoides, the increased infection durations in households with no indoor bathrooms is consistent with reports that poor sanitation facilities increases the risk of A. lumbricoides infections (Strunz EC et al, 2014;Ziegelbauer K et al, 2012). Finally, the association of reduced water access and dirt flooring with increased E. intestinalis trophozoite and fecal cyst counts (Langford TD et al, 2002;Venkatesan et al, 1996).…”

Clearance ofCitrobacter rodentiumRequires B Cells but Not Secretory Immunoglobulin A (IgA) or IgM Antibodies

“…IgA-deficient mice (obtained from J. Nedrud, Case Western Reserve University, Cleveland, Ohio) have a deletion in the I␣ exon, the S␣ switch region, exon 1, and part of exon 2 of the Ig ␣ chain gene (8). These mice are completely deficient in IgA production but have modestly increased levels of IgM and IgG in serum (8,18). Mice deficient in secreted IgM (sIgM), obtained from J. Chen (Massachusetts Institute of Technology, Boston, Mass.…”

The effects of nitric oxide on the immune response during giardiasis

“…75 The infections are normally self-limiting, as immunocompetent hosts can control and typically eradicate G. lamblia, a process that involves T and B-cells. 50,51,76,77 Several studies suggest an important role for B-cells in clearing Giardia infection. For example, infections of humans with G. lamblia result in the production of antigiardial antibodies of the IgA, IgM and IgG isotypes in mucosal secretions and serum.…”