Neutralization of maternal IL-4 modulates congenital protozoal transmission: comparison of innate versus acquired immune responses.
IL-4 levels were modulated in mice to test the hypothesis that induction of a maternal type 1 response would decrease the frequency of congenital Neospora caninum transmission. This hypothesis tested the relationship between IL-4 and both innate and adaptive immunity utilizing two basic experimental designs. In the first, maternal IL-4 was neutralized with mAb during pregnancy in naive mice concomitant with initial, virulent infection. In the second, maternal IL-4 was neutralized before pregnancy concomitant with a priming inoculation consisting of live, avirulent N. caninum tachyzoites followed by virulent challenge during subsequent gestation. In mice that were naive before pregnancy, neutralization of IL-4 during gestational challenge did not result in decreased congenital transmission as measured by PCR performed on 1-day-old neonatal mice. In mice that were primed and modulated before pregnancy, congenital transmission from gestational challenge was significantly decreased compared with control mice. Reduction in transmission constituted a decrease in the numbers of mice transmitting N. caninum and a lower frequency of transmission by individual dams (p < 0.05). Decreased congenital transmission was associated with significantly lower levels of maternal splenocyte IL-4 secretion, lower IL-4 mRNA levels, and higher levels of IFN-gamma secretion. Protected mice had significantly decreased Neospora-specific IgG1 compared with nonmodulated mice. These studies define a relationship between maternal Ag-specific immunity and the frequency of congenital transmission and demonstrate that modulation of type 2 cytokine responses can change the frequency of congenital protozoal transmission.
Long
M T
MT
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA. longm@mail.vetmed.ufl.edu
Baszler
T V
TV
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology; D003048:Coccidiosis / Q000151:congenital / Q000276:immunology* / Q000635:transmission*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007113:Immunity, Innate; D007112:Immunity, Maternally-Acquired; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018688:Neospora / Q000276:immunology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma