51
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      A role for IgG immune complexes during infection with the intracellular pathogen Leishmania

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      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

          We examined the role of immunoglobulin (Ig)G antibodies in mediating host defense to the intracellular parasite, Leishmania. We show that IgG not only fails to provide protection against this intracellular pathogen, but it actually contributes to disease progression. The J H strain of BALB/c mice, which lack IgG because they have a targeted deletion in the Ig heavy chain (J) locus, were more resistant to infection with Leishmania major than were normal BALB/c mice. However, the passive administration of anti-Leishmania IgG caused J H mice to develop large lesions containing high numbers of parasites. Antibody administration correlated with an increase in interleukin (IL) 10 production in lesions, and blocking the murine IL-10 receptor prevented antibody-mediated disease exacerbation. In human patients with active visceral leishmaniasis, high IgG levels are predictive of disease. Patients with ongoing disease had high IgG antibody titers and no delayed-type hypersensitivity (DTH) responses to Leishmania antigens. This pattern was reversed upon disease resolution after treatment, resulting in a decrease in total IgG, which was accompanied by a progressive increase in DTH responsiveness. We conclude that IgG can cause a novel form of immune enhancement due to its ability to induce IL-10 production from macrophages.

          Related collections

          Most cited references57

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

          CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity.

          The long-term persistence of pathogens in a host that is also able to maintain strong resistance to reinfection, referred to as concomitant immunity, is a hallmark of certain infectious diseases, including tuberculosis and leishmaniasis. The ability of pathogens to establish latency in immune individuals often has severe consequences for disease reactivation. Here we show that the persistence of Leishmania major in the skin after healing in resistant C57BL/6 mice is controlled by an endogenous population of CD4+CD25+ regulatory T cells. These cells constitute 5-10% of peripheral CD4+ T cells in naive mice and humans, and suppress several potentially pathogenic responses in vivo, particularly T-cell responses directed against self-antigens. During infection by L. major, CD4+CD25+ T cells accumulate in the dermis, where they suppress-by both interleukin-10-dependent and interleukin-10-independent mechanisms-the ability of CD4+CD25- effector T cells to eliminate the parasite from the site. The sterilizing immunity achieved in mice with impaired IL-10 activity is followed by the loss of immunity to reinfection, indicating that the equilibrium established between effector and regulatory T cells in sites of chronic infection might reflect both parasite and host survival strategies.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Neuroscience. Developmental refining of neuroglial signaling?

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

              Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages.

              Development of the appropriate CD4+ T helper (TH) subset during an immune response is important for disease resolution. With the use of naïve, ovalbumin-specific alpha beta T cell receptor transgenic T cell, it was found that heat-killed Listeria monocytogenes induced TH1 development in vitro through macrophage production of interleukin-12 (IL-12). Moreover, inhibition of macrophage production of IL-12 may explain the ability of IL-10 to suppress TH1 development. Murine immune responses to L. monocytogenes in vivo are of the appropriate TH1 phenotype. Therefore, this regulatory pathway may have evolved to enable innate immune cells, through interactions with microbial pathogens, to direct development of specific immunity toward the appropriate TH phenotype.
                Bookmark

                Author and article information

                Journal
                J Exp Med
                The Journal of Experimental Medicine
                The Rockefeller University Press
                0022-1007
                1540-9538
                7 March 2005
                : 201
                : 5
                : 747-754
                Affiliations
                [1 ]Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742
                [2 ]Department of Biochemistry, Universidade Federal Rio Grande do Norte, Natal RN 59078-970, Brazil
                Author notes

                CORRESPONDENCE David M. Mosser: dmosser@ 123456umd.edu

                Article
                20041470
                10.1084/jem.20041470
                1351290
                15753208
                866dffb5-0226-42cf-a60c-c97457be5511
                Copyright © 2005, The Rockefeller University Press
                History
                : 21 July 2004
                : 10 January 2005
                Categories
                Article

                Medicine
                Medicine

                Comments

                Comment on this article