Systemic and Mucosal Responses to Oral Administration of Excretory and Secretory Antigens from Giardia intestinalis (original) (raw)
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Infection and Immunity, 1986
We analyzed the appearance and level of Giardia muris-specific antibody of immunoglobulin A (IgA), IgG, and IgM isotypes, at weekly intervals, over the course of a 7-week infection in BALB/c and C57BL/6 mice. Using sensitive immunoradiometric assays, we observed that IgA antibody was the only detectable anti-G. muris antibody in intestinal secretions throughout the course of infection. No secreted IgG or IgM anti-G. muris antibody was detected even in concentrated intestinal secretions. The expulsion of G. muris by the mice was associated closely with the appearance and increasing levels of secreted anti-G. muris IgA antibody. Both IgG and IgA serum antibody to G. muris were detected, but no serum IgM antibody was detected. Serum IgA and IgG anti-G. muris antibody remained at high levels up to 10 weeks following clearance of the parasite. An interesting observation indicated that serum IgA antibody to G. muris developed more slowly in response to infection than secreted IgA antibody...
Australian Journal of Experimental Biology and Medical Science, 1983
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. •'•''S-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 hind to the Iectin. wheat germ agglutinin (WGA), and that can be radioiodinated. ln 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 ahle 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 X C3H/He)Fo 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 W^/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 hy examination of the capacity of the intestine to support induced immune responses.
Giardia duodenalis pathogenicity on immunosuppressed animal model
Tropical Biomedicine, 2020
Giardiasis is the major water-borne diarrheal disease present worldwide caused by the common intestinal parasite, Giardia duodenalis. This work aims to investigate the effect of G. duodenalis infection pathogenicity in immunosuppressed animals through histopathological examination. A total of 45 BALB/c mice were divided into four groups; G1 (negative control), G2 (healthy animals exposed to Giardia); G3 (immunosuppressed animals exposed to Giardia), and G4 (non-exposed immunosuppressed animals). Our study revealed that G3 was the most affected group with an infection rate of 100%. The animals showed general weakness, soft stool, and high death rate with severe histopathological changes in the duodenum and mild degenerative changes in hepatic tissues. In G2, the maximal lesions in both duodenum and liver were on the 11 th day. We spotted damage in the villi, edema in the central core, and submucosa, in addition to increased cellular infiltration with inflammation in lamina propria. The presence of the parasites within the villi and the lumen was clear. Most of the hepatocytes revealed hydropic and fatty changes, also dilated congested central veins and edema were observed. G3 changes were more intense than G2 with massive Giardia trophozoites between the intestinal villi, lumen, and extensive fatty liver degeneration. Immune suppression plays a significant role in the severity of injury with the Giardia parasites in duodenum and liver cells.
Giardia lamblia infection induces different secretory and systemic antibody responses in mice
Parasite Immunology, 2005
The adult mouse model of Giardia lamblia infection serves as an excellent animal model to understand the immunological mechanisms involved in the control and clearance of Giardia infection. Little is known about the G. lamblia-specific antigens that stimulate the humoral immune response in this model of giardiasis. We analysed the secretory and systemic antibody responses to G. lamblia during primary and secondary infection in C3H/HeJ adult mice. Faecal IgA and Serum IgG anti-G. lamblia antibodies were observed at week 2 post-infection. Serum IgG responses remained constant over the next several weeks, whereas faecal IgA titres continued to rise from weeks 2–6 post-infection. Western blot analysis revealed that intestinal IgA and serum IgG antibody responses were directed toward several distinct proteins of G. lamblia. Certain proteins appeared to be recognized by both faecal IgA and serum IgG, whereas other antigens were specific for either the secretory or systemic antibody responses. G. lamblia primary and secondary infections were associated with differences in the antibody recognition pattern. The biochemical and immunological characterization of these antigens will help us to better understand the immunobiology of the G. lamblia–host interaction.
The Journal of Immunology
The role of specific serum and milk anti-Giardia muris antibodies in mediation of host-effector responses to this enteric pathogen is unknown. We have investigated antibody-dependent cell-parasite interactions, potentially important as mediators of protection against infection at the mucosal surface. Elicited mouse peritoneal neutrophils and macrophages were incubated with G. muris trophozoites in the presence of either serum or milk antibodies, and their adherence and phagocytosis of the parasites were assessed. The percentage of trophozoites with adherent neutrophils increased significantly in the presence of heat-inactivated immune rabbit serum (93.5% +/- 6.5) and immune mouse milk (54.4% +/- 11.3) and their purified IgG (35.2% +/- 9.7) and secretory IgA fractions (48.0% +/- 12.3) when compared with incubation in RPMI-10% FCS (21.7% +/- 13.9). Similarly, macrophage adherence to trophozoites increased from 49.7% +/- 14.3 in medium alone to respective values of 92.8% +/- 7.1 in imm...
Immune effector responses to an excretory-secretory product of Giardia lamblia
Fems Immunology and Medical Microbiology, 1999
The prior immunisation of mice with purified excretory-secretory product (ESP) led to a complete failure of Giardia lamblia colonisation following challenge inoculation of these animals with trophozoites. The prior immunisation of mice with ESP resulted in a significant stimulation of local immunity as evidenced by a significant enhancement of T helper/inducer activity along with a significant increase in immunoglobulin A-bearing cells. Further, the presence of anti-ESP antibodies in the serum of immunised as well as immunised-challenged animals indicated the stimulation of the systemic lymphoid system. This suggests that the ESP is highly immunogenic and it could be one of the major antigens of G. lamblia responsible for protection against the infection. z
Antigenic variation and the murine immune response to Giardia lamblia
International Journal for Parasitology, 1998
The protozoan parasite Giardia lamblia is an important causative agent of acute or chronic diarrhoea in humans and various animals[ During infection\ the parasite survives the host|s reactions by undergoing continuous antigenic variation of its major surface antigen\ named VSP "variant surface protein#[ The VSPs form a unique family of cysteine!rich proteins that are extremely heterogeneous in size[ The relevance of antigenic variation for the survival in the host has been most successfully studied by performing experimental infections in a combined mother:o}spring mouse system and by using the G[ lamblia clone GS:M!72!H6 "human isolate# as model parasite[ In!vivo antigenic variation of G[ lamblia clone GS:M!72!H6 is characterised by a diversi_cation of the intestinal parasite population into a complex mixture of di}erent variant antigen types[ It could be shown that maternally transferred lactogenic anti!VSP IgA antibodies exhibit cytotoxic activity on the Giardia variant!speci_c trophozoites in suckling mice\ and thus express a modulatory function on the proliferative parasite population characteristics[ Complementarily\ in!vitro as well as in! vivo experiments in adult animals indicated that non!immunological factors such as intestinal proteases may interfere into the process of antigen variation in that they favour proliferation of those variant antigen!type populations which resist the hostile physiological conditions within the intestine[ These observations suggest that an interplay between immunological and physiological factors\ rather than one of these two factor alone\ modulates antigenic diversi_cation of a G[ lamblia population within an experimental murine host and thus in~uences the survival rate and strategy of the parasite[ Þ 0887 Australian Society for Parasitology[ Published by Elsevier Science Ltd[ All rights reserved Keywords] Giardia lamblia^Giardiasis^Variant surface protein^Antigenic variation^Mucosal immune response^Antibody responseÎ ntestinal IgA production^Milk IgA production 0[ Giardia lamblia infections and giardiasis Giardia lamblia "Giardia duodenalis\ Giardia intestinalis# is a zoonotic protozoan parasite which Corresponding author[ Tel] "30# 20 5201273^Fax] "30# 20 5201511^e!mail] nmuellerÝipa[unibe[ch[
Central importance of immunoglobulin A in host defense against Giardia spp
Infection and …, 2002
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.
Secretory IgA antibody responses in Venezuelan children infected with Giardia duodenalis
Journal of tropical …, 2004
We standardized and evaluated an ELISA technique for the detection of total and specific anti-Giardia duodenalis secretory IgA antibodies (slgA). Samples of saliva and serum of 161 Venezuelan schoolchildren were analysed. After stool examination, 66 children were diagnosed to be infected with Giardia duodenalis, 22 with other protozoa, and 73 non-parasitized. The mean (+ 2 SD) values of secretory IgA in the non-parasitized group was considered as the criterion of positivity. The levels of total and specific anti-Giardia slgA were significantly higher in children with Giardia compared with the group with other protozoa (p < 0.01) and the non-parasitized group (p < 0.001). The ELISA technique developed showed values of sensitivity and specificity of 74 and 94 per cent, respectively, a predictive value of 92 per cent for positive samples and 80 per cent for negative samples. Specific anti-Giardia IgA serum levels showed a low sensitivity (57 per cent) and a predictive value for negative samples (53 per cent). Our results suggest that secretory anti-Giardia IgA levels measured in saliva samples may reflect local intestinal IgA responses elicited by these parasites. Thus, determinations of the levels of slgA anti-Giardia could be a useful diagnostic tool for giardiasis in children.