TY - JOUR
T1 - Development of antimalaria immunity in mice lacking IFN-γ receptor 1
AU - Tsuji, Moriya
AU - Miyahira, Yasushi
AU - Nussenzweig, Ruth S.
AU - Aguet, Michel
AU - Reichel, Martin
AU - Zavala, Fidel
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1995
Y1 - 1995
N2 - IFN-γ receptor deficient (IFN-γR) mice, immunized with different developmental stages of malaria parasites, were used to define the mechanisms of protection against the various stages of this infection. IFN-γR mice failed to develop protective immunity against Plasmodium yoelii sporozoites or liver stages, upon immunization with a single dose of irradiated sporozoites, whereas in immunized wild-type mice, parasite development was strongly inhibited. Immunized wild-type mice expressed high levels of inducible nitric oxide synthase (iNOS) mRNA in their liver, upon challenge with viable sporozoites, whereas only background levels of iNOS were detected in immunized IFN-γR mice. In contrast, after immunization with multiple doses of irradiated sporozoites, both IFN-γR and wild-type mice mounted an immune response, which strongly inhibited the development of liver stage parasites. In both types of mice, protection occurred in the absence of appreciable expression of liver iNOS mRNA. As for the course of the erythrocytic phase of infection by nonlethal malaria species, P. yoelii yoelii and P. chabaudi adami, we observed only a moderately prolonged parasitemia in IFN-γR mice compared with wild-type mice, indicating that IFN-γ may only play a modest role in immunity against erythrocytic stages. These results indicate that IFN-γ is the main mediator of the protective mechanism that develops first upon immunization with sporozoites. However, the nature of the anti-parasite mechanism(s) changes in the course of immunization, so that multiple immunizing doses elicit additional protective mechanisms, which are independent of IFN-γ and its receptor
AB - IFN-γ receptor deficient (IFN-γR) mice, immunized with different developmental stages of malaria parasites, were used to define the mechanisms of protection against the various stages of this infection. IFN-γR mice failed to develop protective immunity against Plasmodium yoelii sporozoites or liver stages, upon immunization with a single dose of irradiated sporozoites, whereas in immunized wild-type mice, parasite development was strongly inhibited. Immunized wild-type mice expressed high levels of inducible nitric oxide synthase (iNOS) mRNA in their liver, upon challenge with viable sporozoites, whereas only background levels of iNOS were detected in immunized IFN-γR mice. In contrast, after immunization with multiple doses of irradiated sporozoites, both IFN-γR and wild-type mice mounted an immune response, which strongly inhibited the development of liver stage parasites. In both types of mice, protection occurred in the absence of appreciable expression of liver iNOS mRNA. As for the course of the erythrocytic phase of infection by nonlethal malaria species, P. yoelii yoelii and P. chabaudi adami, we observed only a moderately prolonged parasitemia in IFN-γR mice compared with wild-type mice, indicating that IFN-γ may only play a modest role in immunity against erythrocytic stages. These results indicate that IFN-γ is the main mediator of the protective mechanism that develops first upon immunization with sporozoites. However, the nature of the anti-parasite mechanism(s) changes in the course of immunization, so that multiple immunizing doses elicit additional protective mechanisms, which are independent of IFN-γ and its receptor
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M3 - Article
C2 - 7537305
AN - SCOPUS:0029041936
SN - 0022-1767
VL - 154
SP - 5338
EP - 5344
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -