Coevolution of hosts and microorganisms: an analysis of the involvement of cytokines in host-parasite interactions.
Parasites may employ particular strategies of eluding an immune response by taking advantage of those mechanisms that normally guarantee immunological self-tolerance. Much in the way as it occurs during the establishment of self-tolerance, live pathogens may induce clonal deletion, functional inactivation (anergy) and immunosuppression. At this latter level, it appears that certain pathogens produce immunosuppressive cytokine-like mediators or provoke the host to secrete cytokines that will compromise the anti-parasite immune response. It appears that immune responses that preferentially involve T helper 1 cells (secretors of interleukin-2-and interferon-gamma) tend to be protective, whereas T helper 2 cells (secretors of IL-4, IL-5, IL-6, and IL-10), a population that antagonizes T helper cells, mediate disease susceptibility and are involved in immunopathological reactions. Cytokines produced by T helper 2 cells mediate many symptoms of infection, including eosinophilia, mastocytosis, hyperimmunoglobulinemia, and elevated IgE levels. Administration of IL-2 and IFN-gamma has beneficial effects in many infections mediated by viruses, bacteria, and protozoa. The use of live vaccinia virus might be an avenue for the treatment of or the vaccination against infection. We have found that a vaccinia virus expressing the gene for human IL-2, though attenuated, precipitates autoimmune disease in immunodeficient, athymic mice. Thus, although T helper 1 cytokines may have desired immunostimulatory properties, they also may lead to unwarranted autoaggressive responses.
Williams
O
O
Centro de Biología Molecular del CSIC, Universidad Autónoma de Madrid, Spain.
Gonzalo
J A
JA
Martínez
C
C
Kroemer
G
G
D000818:Animals; D005075:Biological Evolution; D016207:Cytokines / Q000502:physiology* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007155:Immunologic Factors / Q000627:therapeutic use; D007376:Interleukin-2 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D010271:Parasites / Q000276:immunology / Q000502:physiology; D010272:Parasitic Diseases / Q000276:immunology / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014614:Vaccines, Synthetic; D014616:Vaccinia virus
D016207:Cytokines; D007155:Immunologic Factors; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic