Early treatment during a primary malaria infection modifies the development of cross immunity.
We have used a murine model to study the kinetics of cross-protection when a primary infection is halted at different times. We analysed how parasitaemia is modified during a second infection with the homologous parasite, a heterologous parasite, or a mixture of the two. In addition, possible mechanisms involved in cross-protection were analysed. Results show that treatment with pyrimethamine on day 5 during a primary infection with P. chabaudi AS (non-lethal), prevents the generation of cross-protection to a new challenge with lethal P. yoelii 17XL. In contrast, when treatment is on day 7, mice survive a P. yoelii infection. Differences between both groups suggest that in order for 'preimmune' mice to survive a lethal challenge, a predominantly TH2-type response is required, with a higher mRNA expression level of IL-4 and IL-10, and a lower mRNA expression of IFN-gamma. This work shows that an early treatment of a malaria infection produced by a non-lethal parasite drives the immune response towards a loss of cross-protection to further infections, in particular with more virulent parasites. This finding should be taken into account for the development of effective malaria vaccines.
Legorreta-Herrera
M
M
Laboratorio de Immunología Molecular, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónomia de Mexico, Iztapalapa, Mexico. marthal@servidor.unam.mx
Ventura-Ayala
M L
ML
Licona-Chávez
R N
RN
Soto-Cruz
I
I
Hernández-Clemente
F F
FF
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D001835:Body Weight; D003429:Cross Reactions; D015870:Gene Expression; D006454:Hemoglobins / Q000032:analysis; D007110:Immunity, Active; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008288:Malaria / Q000188:drug therapy* / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D018512:Parasitemia; D016788:Plasmodium chabaudi / Q000187:drug effects / Q000276:immunology*; D010967:Plasmodium yoelii / Q000276:immunology*; D011739:Pyrimethamine / Q000008:administration & dosage / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism
D000913:Antibodies, Protozoan; D006454:Hemoglobins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D011739:Pyrimethamine