Helper T cell and antibody responses to infection of CBA mice with Babesia microti.
Helper T cell cytokine and antibody responses were investigated in mice after infection with Babesia microti (King strain). Infection of CBA mice with 106 parasitized erythrocytes resulted in the development of a transitory high parasitaemia which peaked 14 days post infection (DPI), and was resolved at 24 DPI. Th1 responses were activated predominately during the acute phase (6-18 DPI) whereas Th2 responses predominated during the recovery phase (14-28 DPI) as detected by the reverse transcriptase polymerase chain reaction. Increased expression of Th1 cytokines was first detected at 6 DPI (IL-2) and 8 DPI (IFN-gamma) and their peak levels were reached at 12 DPI. After the peak levels were reached, they progressively declined and fell to baseline levels (22 DPI). Increased expression of Th2 cytokines (IL-4 and IL-10) first appeared at 14 DPI, peaked at 20 DPI and Th2 cytokine levels were elevated till the end of the study (28 DPI). Levels of serum IFN-gamma detected by a sandwich ELISA correlated well with IFN-gamma gene expression and were detectable at 8-18 DPI. IgM against B. microti was first detected in serum by ELISA at 4 DPI, and peaked at 10 DPI. The levels of IgM subsequently declined but remained positive at low titre till the end of study. IgG against B. microti was first detected at 8 DPI and peak levels were reached at 24 DPI and remained at that level until the end of study. The results of the present study show that Th1 cytokines predominated in the early inflammatory response and might be involved in control of levels of acute parasitaemia whereas the Th2-associated responses, including expression of IL-4 and IL-10 and the production of parasite-specific IgG, might be the functional means for the reduction and clearance of the parasite from the body. It was concluded that an effective vaccine against Babesia spp. should be designed to induce Th1 responses to maintain the parasitaemia at unfulminating levels and also maintain Th2 responses to clear the parasite from the body.
Chen
D
D
School of Biomedical and Molecular Science, James Cook University of North Queensland, Townsville, Queensland 4811, Australia.
Copeman
D B
DB
Burnell
J
J
Hutchinson
G W
GW
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D000918:Antibody Specificity; D001403:Babesia / Q000472:pathogenicity; D001404:Babesiosis / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D018512:Parasitemia; D012333:RNA, Messenger / Q000032:analysis; D016053:RNA, Protozoan / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D013997:Time Factors
D000913:Antibodies, Protozoan; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D012333:RNA, Messenger; D016053:RNA, Protozoan; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma