Interleukin‐13 in the skin and interferon‐γ in the liver are key players in immune protection in human schistosomiasis

Dessein, Alain; Kouriba, Bourèma; Eboumbou, Carole; Dessein, Hélia; Argiro, Laurent; Marquet, Sandrine; Elwali, Nasr-Eldin M. A.; Rodrigues, Virmondés; Li, Yuesheng; Doumbo, Ogobara K.; Chevillard, Christophe

doi:10.1111/j.0105-2896.2004.00195.x

Cited by 53 publications

(48 citation statements)

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“…The role of IL-13 in S. mansoni-induced fibrosis is well established for mice (8,9,10,17,25,31,32), results which have been confirmed for humans (12,14,30). In contrast, IL-4 does not seem to be essential for the liver fibrosis induced by egg deposition (22).…”

Section: Discussionmentioning

confidence: 96%

Experimental Infection withSchistosoma mansoniin CCR5-Deficient Mice Is Associated with Increased Disease Severity, as CCR5 Plays a Role in Controlling Granulomatous Inflammation

Souza

Pereira

et al. 2011

Infect Immun

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The plasma level of the chemokine CCL3 is elevated in patients with chronic severe schistosomiasis mansoni. We have previously shown that CCL3؊/؊ mice with experimental infection showed diminished pathology and worm burden compared to those of wild-type (WT) mice. To elucidate further the role of CC chemokines during schistosomiasis mansoni infection, we evaluated the course of infection in C57BL/6J mice deficient in CCR5, one of the receptors for CCL3. The CCR5 deficiency proved to be remarkably deleterious to the host, since mortality rates reached 70% at 14 weeks postinfection in CCR5 ؊/؊ mice and 19% in WT mice. The increased lethality was not associated with an increased parasite burden, since similar numbers of eggs and adult worms were found in mice from both groups. Liver granulomas of chronically infected CCR5 ؊/؊ mice were larger and showed greater numbers of cells and collagen deposition than liver granulomas from WT mice. This was associated with higher levels of production of intereleukin-5 (IL-5), IL-13, CCL3, and CCL5 in infected CCR5 ؊/؊ mice than in infected WT mice. Moreover, at 8 weeks after infection, just before changes in pathology and mortality, the numbers of FoxP3-positive cells were lower in liver granulomas of CCR5 ؊/؊ mice than in WT mice. In conclusion, the CCR5 deletion is deleterious to mice infected with Schistosoma mansoni, and this is associated with enhanced fibrosis and granulomatous inflammation.

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Section: Discussionmentioning

confidence: 96%

Experimental Infection withSchistosoma mansoniin CCR5-Deficient Mice Is Associated with Increased Disease Severity, as CCR5 Plays a Role in Controlling Granulomatous Inflammation

Souza

Pereira

et al. 2011

Infect Immun

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“…[15][16][17][18] Interferon gamma (IFN-␥) is also recognized as a cytokine eliciting effects antagonistic to TGF-␤, and antifibrotic activity has been reported in a variety of organs. 19,20 The incubation of human proximal tubular epithelial cells with IFN-␥ inhibited TGF-␤-mediated ␣-smooth muscle actin expression and blunted TGF-␤-induced fibronectin and plasminogen activator inhibitor-1 (PAI-1) expression. 21 Adeno-associated virus-mediated overexpression of human IFN-␥ inhibited the activation of isolated HSCs in CCl 4 -treated rats.…”

mentioning

confidence: 99%

Profibrogenic transforming growth factor-β/activin receptor-like kinase 5 signaling via connective tissue growth factor expression in hepatocytes

et al. 2007

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Connective tissue growth factor (CTGF) is important for transforming growth factor-␤ (TGF-␤)-induced liver fibrogenesis. Hepatic stellate cells have been recognized as its major cellular source in the liver. Here we demonstrate the induction of CTGF expression in hepatocytes of damaged livers and identify a molecular mechanism responsible for it. CTGF expression was found by immunohistochemistry in bile duct epithelial cells, hepatic stellate cells, and hepatocytes in fibrotic liver tissue from patients with chronic hepatitis B infection. Similarly, CTGF expression was induced in hepatocytes of carbon tetrachloride-treated mice. CTGF expression and secretion were detected spontaneously in a medium of hepatocytes after 3 days of culture, which was enhanced by stimulation with TGF-␤. TGF-␤-induced CTGF expression was mediated through the activin receptor-like kinase 5 (ALK5)/ Smad3 pathway, whereas activin receptor-like kinase 1 activation antagonized this effect. CTGF expression in the liver tissue of TGF-␤ transgenic mice correlated with serum TGF-␤ levels. Smad7 overexpression in cultured hepatocytes abrogated TGF-␤-dependent and intrinsic CTGF expression, indicating that TGF-␤ signaling was required. In line with these data, hepatocyte-specific transgenic Smad7 reduced CTGF expression in carbon tetrachloride-treated animals, whereas in Smad7 knockout mice, it was enhanced. Furthermore, an interferon gamma treatment of patients with chronic hepatitis B virus infection induced Smad7 expression in hepatocytes, leading to decreased CTGF expression and fibrogenesis. Conclusion: Our data provide evidence for the profibrogenic activity of TGF-␤ directed to hepatocytes and mediated via the up-regulation of CTGF. We identify ALK5-dependent Smad3 signaling as the responsible pathway inducing CTGF expression, which can be hindered by an activated activin receptor-like kinase 1 pathway and completely inhibited by

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“…It has been argued that it makes biological sense for IL-13, IL-5, and IFN-γ to have a central role in the response to infection with Schistosoma spp. 16,30 Because of IL-13's function in signaling B cells to switch to IgE production and IL5's and IL-13's principal role in recruiting and activating eosinophils, these cytokines are important in the initial response to invading cercaria and later on, to schistosomula. 30 Eosinophilia is known to be associated with Katayama syndrome, 17,19 and the stronger IL-5 and IL-13 responses that we found may reflect stronger activation of eosinophils at the time of infection in the travelers with Katayama syndrome.…”

Section: Discussionmentioning

confidence: 99%

The Immune Response to Schistosome Antigens in Formerly Infected Travelers

Soonawala¹,

Geerts²,

Mos³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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We investigated the type and strength of the immune response to schistosome antigens in a group of 20 Dutch travelers who had been infected with Schistosoma spp. during a group visit to Mali in 1991 and 8 non-infected controls. At the time, 9 had Katayama syndrome (KS), and 11 remained asymptomatic. All had been treated with praziquantel. Eight years later, serology remained positive in all 20 formerly infected travelers. The lymphocyte proliferative responses and cytokine responses (interleukin 13 [IL-13], IL-10, and interferon [IFN-γ] responses to soluble egg antigens and the IL-13, IL-10, and IL-5 response to adult worm antigen) were stronger in the travelers than in the controls and tended to be stronger in those with KS compared with those who had remained asymptomatic. In conclusion, Schistosoma infection induced a memory immune response, and people who experienced KS tended to have a stronger immune response to schistosome antigens than their asymptomatic counterparts.

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Interleukin‐13 in the skin and interferon‐γ in the liver are key players in immune protection in human schistosomiasis

Abstract: International audienceno abstrac

Cited by 53 publications

References 100 publications

Experimental Infection withSchistosoma mansoniin CCR5-Deficient Mice Is Associated with Increased Disease Severity, as CCR5 Plays a Role in Controlling Granulomatous Inflammation

Experimental Infection withSchistosoma mansoniin CCR5-Deficient Mice Is Associated with Increased Disease Severity, as CCR5 Plays a Role in Controlling Granulomatous Inflammation

Profibrogenic transforming growth factor-β/activin receptor-like kinase 5 signaling via connective tissue growth factor expression in hepatocytes

The Immune Response to Schistosome Antigens in Formerly Infected Travelers

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