Mast Cell-Dependent Control ofGiardia lambliaInfections in Mice

Abstract

Mast cells are important for protective immunity to intestinal helminth infections and as mediators of allergic disease. Their role in protozoan infections is less well described. We have therefore analyzed mast cell responses and parasite control in mice infected with the protozoan Giardia lamblia. We also measured immunoglobulin A (IgA) responses to the parasite, as IgA can have a protective role in this model. c-kit w/wv mice failed to make parasite-specific IgA, mount a mast cell response, or eliminate the infection. Anti-c-kittreated C57BL/6 mice had normal IgA responses, lacked mast cell responses, had reduced interleukin-6 (IL-6) mRNA in the small intestine, and failed to control the infection within 10 days. IL-9-deficient mice had a significant but reduced mast cell response and still controlled the infection within 2 weeks. Interestingly, IL-6-deficient mice had enhanced mast cell responses yet failed to rapidly control the infection. However, prevention of mast cell responses in IL-6-deficient mice by anti-c-kit treatment did not lead to parasite elimination. Both IL-6-and IL-9-deficient mice had normal IgA production. IL-6-deficient mice had significant serum levels of mast cell mediators, histamine and mast cell protease 1, following infection. Together, these results show that mast cells are important for the rapid control of Giardia infections in mice. Furthermore, they show that IL-6 is not necessary for these mast cell responses. Instead, they suggest that mast cell production of IL-6 appears to be important for control of this infection.

Resistance to reinfection in mice as a vaccine model for giardiasis

“…Our data indicate that IFNγ predominates 5 d after infection in C57BL/6 mice. This is consistent with reports of IFNγ production by peripheral blood and lamina propria lymphocytes from non-infected humans in response to Giardia antigen 25 and by conA stimulated mesenteric lymph node cells from BALB/c or C57BL/10 mice infected with G. muris. 26,27 It is also consistent with the elevated levels of IFNγ seen in sera from patients.…”

Neuronal Nitric Oxide Synthase Is Necessary for Elimination of Giardia lamblia Infections in Mice

“…For example, although IgA against the parasite is clearly toxic in vitro, B cell-and IgA-deficient mice eliminate 90% or more of the parasites between 1 and 2 wk after infection (4,5). This contrasts with SCID mice and c-kit w/wv mice that maintain infections for at least several months and IL-6-deficient mice that eliminate infections between 4 and 8 wk after infection (5,6,13). This probably reflects the fact that elimination of Giardia occurs through several redundant mechanisms, and it is only in mouse mutants deficient in multiple or nonredundant mechanisms that a clear phenotype is observed.…”

“…These include antimicrobial peptides, NO, and mast cell products (8 -12). We have recently found that mice that are unable to produce a mast cell response are deficient in the elimination of Giardia infections (13). In contrast, Eckmann (3) reported that mice lacking functional ␣-defensins due to deletion of the gene for matrilysin control G. muris infections as well as wild-type mice.…”

Inducible nitric oxide synthase in duodenum of children with Giardia lamblia infection.

“…Therefore it has been found to be cytostatic but not cytotoxic for Giardia lamblia trophozoites [18]. Production NO together with other antigiardial host defense: antimicrobial peptides such as defensins and lactoferins [25][26][27], B cells [1,9], mast cells [28] and particularly secretory IgA antibodies [1,29] have an influence on duration of infection and severity of symptoms, leading in the majority of cases to self-limiting of the disease. This is probably the reason of lack of morphological alternations and the intensive immunoexpression for iNOS, the basic enzyme in synthesis of NO, in the biopsies of 5 children with Giardia lamblia infection.…”