Interleukin-6-Deficient Mice Are Highly Susceptible to<i>Giardia lamblia</i>Infection but Exhibit Normal Intestinal Immunoglobulin A Responses against the Parasite

Bienz, Marianne; Dai, Wen Juan; Welle, Monika Maria; Gottstein, Bruno; Müller, Norbert

doi:10.1128/iai.71.3.1569-1573.2003

Cited by 78 publications

(68 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, a lower activation or damage to host cell should be associated with a low inflammation that progresses in giardiasis. Previous work using mouse models to determine the role of various cytokines in immunity to Giardia have shown that IL-6 plays a critical role in the control of primary infections with this parasite (Bienz et al, 2003;Zhou et al, 2003). Here, we have analysed whether MVs release by trophozoites should alter dendritic cells, which are a family of professional antigen-presenting cells (APCs), that reside in all peripheral tissues in an immature state, capable of antigen uptake and processing.…”

Section: Microvesicles From Giardia Intestinalis Modulate Dendritic Cmentioning

confidence: 99%

Microvesicles released from Giardia intestinalis disturb host-pathogen response in vitro

Evans-Osses

Mojoli

Monguió‐Tortajada

et al. 2017

European Journal of Cell Biology

View full text Add to dashboard Cite

a b s t r a c tGiardia intestinalis (G.I), is an anaerobic protozoan and the aetiological agent of giardiasis, a diarrhoea present worldwide and associated with poverty. G.I has a simple life cycle alternating between cyst and trophozoite. Cysts are transmitted orally to the stomach and transform to trophozoites in the intestine by a multifactorial process. Recently, microvesicles (MVs) have been found to be released from a wide range of eukaryotic cells. We have observed a release of MVs during the life cycle of G.I., identifying MVs from active trophozoites and from trophozoites differentiating to the cyst form. The aim of the current work was to investigate the role of MVs from G.I in the pathogenesis of giardiasis. MVs from log phase were able to increase the attachment of G. intestinalis trophozoites to Caco-2 cells. Moreover, MVs from G. intestinalis could be captured by human immature dendritic cells, resulting in increased activation and allostimulation of human dendritic cells. Lipid rafts participate in the MV biogenesis and in the attachment to Caco-2 cells. Nevertheless, proteomic analysis from two types of MVs has shown slight differences at the protein levels. An understanding of biogenesis and content of MVs derived from trophozoites might have important implications in the pathogenesis of the disease.

show abstract

Section: Microvesicles From Giardia Intestinalis Modulate Dendritic Cmentioning

confidence: 99%

Microvesicles released from Giardia intestinalis disturb host-pathogen response in vitro

Evans-Osses

Mojoli

Monguió‐Tortajada

et al. 2017

European Journal of Cell Biology

View full text Add to dashboard Cite

show abstract

“…It is unclear what immune mechanisms are responsible for effective control of infections (2,3). Although IgA has been shown to have a role in controlling infections (4), it is clear that IgA-independent mechanisms are also able to eliminate Giardia and that IL-6 appears to be pivotal for these pathways (5)(6)(7).…”

mentioning

confidence: 99%

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

Zhou

Singer

2006

The Journal of Immunology

View full text Add to dashboard Cite

NO produced by inducible NO synthase (NOS2) is important for the control of numerous infections. In vitro, NO inhibits replication and differentiation of the intestinal protozoan parasite Giardia lamblia. However, the role of NO against this parasite has not been tested in vivo. IL-6-deficient mice fail to control Giardia infections, and these mice have reduced levels of NOS2 mRNA in the small intestine after infection compared with wild-type mice. However, NOS2 gene-targeted mice and wild-type mice treated with the NOS2 inhibitor N-iminoethyl-l-lysine eliminated parasites as well as control mice. In contrast, neuronal NOS (NOS1)-deficient mice and wild-type mice treated with the nonspecific NOS inhibitor NG-nitro-l-arginine methyl ester and the NOS1-specific inhibitor 7-nitroindazole all had delayed parasite clearance. Finally, Giardia infection increased gastrointestinal motility in wild-type mice, but not in SCID mice. Furthermore, treatment of wild-type mice with NG-nitro-l-arginine methyl ester or loperamide prevented both the increased motility and the elimination of parasites. Together, these data show that NOS1, but not NOS2, is necessary for clearance of Giardia infection. They also suggest that increased gastrointestinal motility contributes to elimination of the parasite and may also contribute to parasite-induced diarrhea. Importantly, this is the first example of NOS1 being involved in the elimination of an infection.

show abstract

“…As a consequence, blockade of IL-6 or IL-6 signaling has a profound impact on innate and acquired immune responses. Impaired IL-6 function causes enhanced susceptibility of mice to infection with various pathogens (6)(7)(8)(9)(10)(11)(12)(13)(14)(15) but also results in protection in several mouse models for chronic inflammatory diseases (16)(17)(18). Not surprisingly, IL-6 signaling is also an important target of intervention in chronic inflammatory human diseases such as rheumatoid arthritis and Crohn's disease (19).…”

mentioning

confidence: 99%

IL-6 Controls the Innate Immune Response against Listeria monocytogenes via Classical IL-6 Signaling

Hoge

Yan

Jänner

et al. 2013

The Journal of Immunology

128

107

View full text Add to dashboard Cite

The cytokine IL-6 plays a protective role in immune responses against bacterial infections. However, the mechanisms of IL-6–mediated protection are only partially understood. IL-6 can signal via the IL-6R complex composed of membrane-bound IL-6Rα (mIL-6Rα) and gp130. Owing to the restricted expression of mIL-6Rα, classical IL-6 signaling occurs only in a limited number of cells such as hepatocytes and certain leukocyte subsets. IL-6 also interacts with soluble IL-6Rα proteins and these IL-6/soluble IL-6Rα complexes can subsequently bind to membrane-bound gp130 proteins and induce signaling. Because gp130 is ubiquitously expressed, this IL-6 trans-signaling substantially increases the spectrum of cells responding to IL-6. In this study, we analyze the role of classical IL-6 signaling and IL-6 trans-signaling in the innate immune response of mice against Listeria monocytogenes infection. We demonstrate that L. monocytogenes infection causes profound systemic IL-6 production and rapid loss of IL-6Rα surface expression on neutrophils, inflammatory monocytes, and different lymphocyte subsets. IL-6–deficient mice or mice treated with neutralizing anti–IL-6 mAb displayed impaired control of L. monocytogenes infection accompanied by alterations in the expression of inflammatory cytokines and chemokines, as well as in the recruitment of inflammatory cells. In contrast, restricted blockade of IL-6 trans-signaling by application or transgenic expression of a soluble gp130 protein did not restrain the control of infection. In summary, our results demonstrate that IL-6Rα surface expression is highly dynamic during the innate response against L. monocytogenes and that the protective IL-6 function is dependent on classical IL-6 signaling via mIL-6Rα.

show abstract

Interleukin-6-Deficient Mice Are Highly Susceptible toGiardia lambliaInfection but Exhibit Normal Intestinal Immunoglobulin A Responses against the Parasite

Cited by 78 publications

References 23 publications

Microvesicles released from Giardia intestinalis disturb host-pathogen response in vitro

Microvesicles released from Giardia intestinalis disturb host-pathogen response in vitro

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

IL-6 Controls the Innate Immune Response against Listeria monocytogenes via Classical IL-6 Signaling

Contact Info

Product

Resources

About