10
views
0
recommends
+1 Recommend
2 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Differential induction of Th2- And Th1-associated responses by filarial antigens and endosymbiotic Wolbachia in a murine model of river blindness

      Read this article at

      ScienceOpenPublisher
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Immune responses to filarial parasites like the river blindness inducing Onchocerca volvulus are obscured by combined reactions to the filarial nematodes themselves and their endosymbiont bacteria Wolbachia. Overall, infection with filarial nematodes induces a strong Th2 response characterized by IL-5 production and to a lesser degree a Th1 response and IFNγ production. Neutrophil and eosinophil infiltration into the corneal stroma are hallmark features of Onchocerca volvulus stimulation in a mouse model of river blindness. To determine the splenic and corneal response to filarial antigens in the absence of Wolbachia, C57BL/6 mice were immunized subcutaneously with either endosymbiotic Wolbachia alone, a soluble extract from the filaria Acanthocheilonema viteae that does not contain Wolbachia, or both, and injected into the corneal stroma. Neutrophil and eosinophil infiltration into the cornea was assessed by immunohistochemistry. In addition, Th1- and Th2-associated responses to filaria or Wolbachia were investigated by determining IL-5 and IFN-γ production by splenocytes. We found that A. viteae in the absence of Wolbachia induced IL-5 production and eosinophil infiltration, but not IFN-γ. Conversely, Wolbachia induced IFN-γ production and no migration of eosinophils. There was no difference in neutrophil infiltration. Together, these findings demonstrate a distinct Th-associated phenotype induced by filaria and Wolbachia.

          Related collections

          Most cited references26

          • Record: found
          • Abstract: found
          • Article: not found

          Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism.

          Recently, the transcription factor GATA-3 was shown to be selectively expressed in Th2 but not Th1 cells and to augment Th2-specific cytokines. Here, we show that loss of GATA-3 expression by developing Th1 cells requires IL-12 signaling through Stat4 and does not simply result from an absence of IL-4. Moreover, we demonstrate a novel role for GATA-3 in directly repressing Th1 development distinct from its positive actions on Th2-specific cytokines. GATA-3 inhibits Th1 cytokines by a cell-intrinsic mechanism that is not dependent on IL-4 and that may involve repression of IL-12 signaling. Thus, GATA-3 expression and IL-12 signaling are mutually antagonistic, which facilitates rapid dominance of one pathway during early Th development, producing a stable divergence in cytokine profiles.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The role of endosymbiotic Wolbachia bacteria in the pathogenesis of river blindness.

            Parasitic filarial nematodes infect more than 200 million individuals worldwide, causing debilitating inflammatory diseases such as river blindness and lymphatic filariasis. Using a murine model for river blindness in which soluble extracts of filarial nematodes were injected into the corneal stroma, we demonstrated that the predominant inflammatory response in the cornea was due to species of endosymbiotic Wolbachia bacteria. In addition, the inflammatory response induced by these bacteria was dependent on expression of functional Toll-like receptor 4 (TLR4) on host cells.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Inducible expression of the proallergic cytokine thymic stromal lymphopoietin in airway epithelial cells is controlled by NFkappaB.

              The epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) is important for the initiation of allergic airway inflammation through a dendritic cell-mediated T helper 2 response. To identify the factors that control TSLP expression, we examined the ability of inflammatory mediators to regulate TSLP production in human airway epithelial cells. We found that both IL-1beta and TNF-alpha were capable of inducing rapid TSLP production in primary human bronchial airway epithelial cells. We further characterized the human TSLP gene promoter, using two human epithelial cell lines, 16HBEo(-) and A549, and showed that IL-1beta- and TNF-alpha-mediated human TSLP promoter activation in these cells was mediated by an upstream NFkappaB site. Mutation of this NFkappaB site abolished activation, as did overexpression of a dominant-negative version of IkappaB kinase (IKK)beta (a kinase acting on IkappaB, the inhibitor of NFkappaB). Interestingly, human TSLP mRNA levels were also increased after exposure to Toll-like receptor (TLR) 2, TLR8, and TLR9 ligands, further supporting an important role for NFkappaB in TSLP gene regulation. Similarly, analysis of the mouse TSLP gene promoter revealed the presence of a similarly situated NFkappaB site that was also critical for IL-1beta-inducible expression of mouse TSLP. Taken together, these results demonstrate that the inflammatory mediators IL-1beta and TNF-alpha regulate human TSLP gene expression in an NFkappaB-dependent manner.
                Bookmark

                Author and article information

                Journal
                1886
                122234
                European Journal of Microbiology and Immunology
                Akadémiai Kiadó
                2062-509X
                2062-8633
                1 June 2012
                13 June 2012
                : 2
                : 2 ( otherID: K022535X4502 )
                : 134-139
                Affiliations
                [ 1 ] Case Western Reserve University Case Medical Center Department of Ophthalmology and Visual Sciences Cleveland Ohio USA
                [ 2 ] University Hospital Bonn Institute for Medical Microbiology, Immunology and Parasitology Bonn Germany
                [ 3 ] University Hospital Bonn Institute for Medical Microbiology, Immunology and Parasitology Sigmund-Freud-Str. 25 53105 Bonn Germany
                Article
                58264637X1578550
                10.1556/eujmi.2.2012.2.6
                b02156e0-026c-40c8-8e30-b72d7fd9b9eb
                Categories
                Original Articles

                Medicine,Immunology,Health & Social care,Microbiology & Virology,Infectious disease & Microbiology
                neutrophils,eosinophils,IL-5,IFNγ,cornea, Acanthocheilonema , Wolbachia ,river blindness,filaria, Onchocerca

                Comments

                Comment on this article