Antibody responses in pregnancy-induced transmammary transmission of Ancylostoma caninum hookworm larvae

Third stage larvae of the Ancylostoma caninum hookworm nematode have the ca pacity to infect a dog, abort the normal maturation pathway to become blood -feeding intestinal worms, and instead distribute throughout the body in a developmentally arrested state that is relatively resilient to most chemoth erapeutic agents. During pregnancy, a percentage of the arrested larvae rea ctivate and transmit via the mammary glands to infect the nursing puppies w ith resulting iron-deficiency anemia and potential mortality. To determine if the suppression of parasite-specific antibody responses during pregnancy facilitates the reactivation and transmammary transfer of hookworm larvae, a murine model of A. caninum infection was used to compare the infected ve rsus uninfected animals that were either bred or not bred. Initial comparis ons of genetically divergent BALB/c versus C57BL/6 mice showed that both th e strains mounted strong Th2 biased IgG1 and IgE antibody responses to A. c aninum infection. Using the BALB/c strain for the breeding analyses, it was confirmed that larval transfer to the mouse pups only occurred during the post-partum lactational period. In the darns, levels of total and antigen-s pecific IgG1 and total IgE were highly correlated with parasite burden. Dur ing most phases of pregnancy and lactation, infected dams had lower total I gG1, IgG2a and IgE levels as compared to unbred mice at comparable times po stinfection; this downward modulation of antibody responses supports the es tablished dogma of a generalized immunosuppression associated with pregnanc y. However, at parturition and postpartum lactation, antigen-specific IgG1 levels measured at 1:5000 serum dilutions were comparable between bred and unbred mice, and antigen-specific IgG2a levels at 1:100 serum dilutions wer e also not significantly different except for a marginal reduction in the b red mice at the lactational timepoint. The comparable anti-ii. caninum IgG1 levels between bred and unbred mice, and low correlation between IgG2a lev els and larval burden suggest that parasite-specific antibody responses do not play a major role in the pregnancy-associated transmammary transmission of A. caninum larvae. This conclusion does not rule out the possibility th at underlying fluxes in the levels of specific cytokines associated with pr egnancy and infection may be involved in the process of larval reactivation and transmission. (C) 1999 Elsevier Science B.V. All rights reserved.