AN EXAMINATION OF DIFFERENCES IN SERUM ANTIBODY SPECIFICITIES AND HYPERSENSITIVITY REACTIONS AS CONTRIBUTING FACTORS TO CHRONIC INFECTION WITH THE INTESTINAL PROTOZOAN PARASITE, GIARDIA MURIS, IN MICE

Abstract

Summary After oral administration of cysts of the intestinal protozoan parasite, Giardia muris, young male C3H/He mice are chronically infected, whereas BALB/c mice demonstrate a rapidly resolving pattern of infection. Both strains of mice injected with trophozoites in adjuvant and challenged orally with cysts develop serum antibodies to numerous trophozoite proteins. A limited number of these protein antigens was differenliatly immunoprecipitated by sera from resistant BALB/c and susceptible C3H/He mice exposed to G. muris. 35S‐methionine‐labelled protein antigens better recognized by immune BALB/c sera included molecules of relative mobility (Mr) 82,000 and a series of proteins of Mr 25,000 to 32,000, Differential recognition extended to a subset of solubilized trophozoite antigens that bind to the Iectin. wheat germ agglutinin (WGA), and that can be radio‐iodinated. In particular, a complex of 4 acidic protein antigens of approximate Mr 32,000. and designated collectively as Gm32, was better recognized by immune BALB/c serum than C3H/He serum. Isolated WGA‐binding antigens were not able to consistently vaccinate BALB/c mice against subsequent G. muris infection. Moreover, preliminary evidence has been obtained that lack of antibody responsiveness to Gm32 does not segregate strictly with susceptibility to chronic infection in (BALB/c × C3H/He)F2 mice. These data, plus the observation that drug‐cured C3H/He mice are highly resistant to reinfection, has led to examination of whether mice differ in the capacity of the intestines to support inflammatory responses. Mast cell deficient Wf/Wf mice, unlike wild‐type litter‐mates, developed chronic giardiasis although no reconstitution of resistance has yet been achieved with inocula of bone marrow cells from +/+ mice. BALB/c mice injected with the antihistamine and antiserotonin drug, cyproheptadine, also showed prolonged infections with G. muris. The data suggest that analysis of specificity differences in immune responses of mice varying in susceptibility to intestinal parasites must be supplemented by examination of the capacity of the intestine to support induced immune responses.

Mast Cell-Dependent Control ofGiardia lambliaInfections in Mice

“…A previous study with c-kit w/wf mice infected with G. muris observed prolonged infections in this model (8). They were unable to restore immunity, however, by adoptive transfer of bone marrow-derived mast cells.…”

“…In this phase of the infection, parasite control requires IL-6 and normally occurs within the first 2 weeks (2, 36). Since mast cells have been suggested to control G. muris infections (8,34), we wanted to determine whether mast cells were involved in the early control of G. lamblia infections and how mast cell responses were related to IL-6. We therefore began by infecting genetically mast cell-deficient c-kit w/wv mice with G. lamblia and determining whether they were able to control the infection.…”

“…Infections in gerbils with G. lamblia or in mice with G. muris have shown that mast cells accumulate in the small intestine following infection (15,20,34). In addition, mast cell-deficient (c-kit w/wf ) mice were unable to control G. muris infections (8), suggesting that mast cell responses may be involved in controlling these infections. However, c-kit mutant animals exhibit multiple defects including anemia, abnormal ␥␦ T cell development, and an absence of intestinal pacemaking activity (13,26,28).…”

“…Cyproheptadine (an antagonist of histamine H1 receptors) treatment prolonged infections with G. muris, suggesting that histamine release from mast cells may be involved in Giardia immunity (34). Importantly, attempts to reconstitute the mast cell response in the c-kit w/wf mice by adoptive transfer of bone marrow mast cells did not restore resistance to infection (8), and cyproheptadine has numerous effects unrelated to its antihistaminic properties, making it difficult to precisely implicate mast cells in resistance to Giardia infection based on these data.…”

Mast Cell-Mediated Changes in Smooth Muscle Contractility during Mouse Giardiasis

“…Significant mast cell responses during Giardia infections have been observed in several experimental systems, and these were also shown to be important for parasite elimination (8,16,21). Mast cell responses have been seen also in numerous intestinal helminth infection models, where they participate variably in parasite elimination, depending on the particular parasite under study (5,24).…”