Production of gamma interferon in mice immune to Rickettsia tsutsugamushi

Abstract

C3H/He mice immunized by subcutaneous infection with Rickettsia tsutsugamushi Gilliam were examined for the production of immune interferon after intravenous administration of irradiated strain Gilliam antigen, in supernatants of immune lymphocytes stimulated with specific antigen, and after a secondary challenge with viable rickettsiae. Mice administered various doses of irradiated whole-organism antigen 28 days after immunization showed circulating levels of interferon which peaked 4 h after inoculation and were antigen dose dependent. The interferon produced was pH 2 sensitive and stable at 56 degrees C for 1 h and was neutralized by antiserum directed against immune, but not against alpha/beta, interferon. The production of another lymphokine, macrophage migration inhibition factor, paralleled that of interferon. The interferon produced by cultures of spleen cells obtained from immune animals was antigen specific and dose dependent. Peak levels were obtained 48 to 72 h after the addition of antigen. The interferon produced by spleen cell cultures after stimulation with Gilliam antigen was characterized as immune interferon by the same physical and antigenic criteria used for serum interferon. Interferon was produced in vitro by the Thy-1.2+ lymphocyte and required the presence of a spleen-adherent cell population. Immune mice produced high circulating levels of immune interferon after intraperitoneal challenge with viable rickettsiae, which suggested a possible role for interferon in the resistance of immune mice to rechallenge with R. tsutsugamushi.

Interferon‐gamma and resistance to bacterial infections

“…A role for IFN-)I in immune resistance to rickettsia infection is suggested by the demonstration of IFN-y production in mice in response to challenge with R. tsutsugamushi and the correlation between peak IFN-y responses and clearance of rickettsemia (87,88). In addition, administration of monoclonal antibody raised against MuIFN-y to mice infected with R. conorii has been shown to exacerbate infection (6 1).…”

Immunosuppression associated with the development of chronic infections with Rickettsia tsutsugamushi: adherent suppressor cell activity and macrophage activation

“…This chronic infection is thought to persist for the life of the animal, suggesting that the rickettsiae are able to survive in the face of an immune response which is demonstrable at the same times (16,32,33). The immunity which develops in response to infection consists of a cell-mediated immunity as measured by a delayed-type hypersensitivity (15), antigen-induced lymphocyte proliferation (16), lymphokine production (27,28), and the development of lymphocytes capable of transferring protective immunity to naive animals (33), as well as a T-dependent antibody response (13).…”

Induction of Protective Immunity Against Scrub Typhus With a 56-Kilodalton Recombinant Antigen Fused With a 47-Kilodalton Antigen of Orientia Tsutsugamushi Karp

“…32 This has been demonstrated by passive transfer of resistance with T cells, 33 development of DTH, 34 and in vitro cytokine secretion of T cells in response to O. tsutsugamushi antigens. 10,11,13,35 Th1 cells have been shown to be responsible for the DTH response, which has been found to correlate with resistance to lethal challenge in mice infected with scrub typhus. 34,36 The proliferative level of splenic cells from mice immunized with Sta56-47 antigen was much higher than that in Sta56-or Sta47-immunized mice in response to homologous antigens.…”

“…Previous studies reported that protective immunity against scrub typhus was induced with irradiated whole cells of O. tsutsugamushi. 10 However, the use of the irradiated vaccine in humans seems to be impractical because the large-scale culture and purification of this obligate intracellular microorganism is timeconsuming and expensive. Therefore, the recombinant proteins produced in Escherichia coli or other organisms will most likely be the future vaccines against scrub typhus.…”