The immune response to Plasmodium chabaudi malaria in interleukin-4-deficient mice.
Interleukin(IL)-4 promotes the development of T helper (TH)2 cells, induces immunoglobulin class switching to IgG1 and is thought to be essential for switching to IgE. During a primary infection with the erythrocytic stages of Plasmodium chabaudi chabaudi, TH1 and TH2 cells specific for the parasite appear sequentially as infection progresses. To dissect the possible role of TH2 responses at the later stages of infection, mice with a targetted disruption of the IL-4 gene were infected with P. chabaudi. IL-4-deficient mice were able to control and clear a primary infection, although recrudescent parasitemias were significantly higher in these mice compared with wild-type littermates; demonstrating that IL-4 per se is not required for parasite elimination. To evaluate the actual impairment of TH2 functions in the absence of IL-4 in vivo during an infection with P. chabaudi; the cellular and humoral responses to the parasite generated in vitro and in vivo were compared in the two types of mice. Our data indicate that in vitro TH1 responses and ex vivo IL-12 mRNA levels were sustained in the IL-4-deficient mice compared with wild-type littermates. Correspondingly, TH2-associated cytokine mRNA such as IL-5 and IL-6, but not IL-10, were reduced early in infection in the deficient animals. However, these cytokines were expressed at comparable levels at the later stages of infection in both types of mice. Reflecting these differences in TH function, IgG1 responses were decreased in vitro and delayed in vivo, whereas IgG2a and IgG2b responses appeared earlier in vivo in the deficient mice. Strikingly, IgE secretion was not blocked in vivo in the deficient mice; the onset of the synthesis of IgE mRNA was delayed during infection and the amount of circulating IgE was five times lower than in the wild-type littermates after 5 weeks of infection. All these impairments of TH2-related activities were insufficient to affect parasite clearance in the deficient mice, probably due to the fact that such activities were only delayed and could take place normally at the later stages of infection.
von der Weid
T
T
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Kopf
M
M
Köhler
G
G
Langhorne
J
J
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000917:Antibody Formation; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D007132:Immunoglobulin Isotypes / Q000276:immunology; D015847:Interleukin-4 / Q000172:deficiency*; D008211:Lymphocyte Cooperation; D008288:Malaria / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016788:Plasmodium chabaudi / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000913:Antibodies, Protozoan; D016207:Cytokines; D017931:DNA Primers; D007132:Immunoglobulin Isotypes; D012333:RNA, Messenger; D015847:Interleukin-4