Effect Of Host Immunity And Co-Infection On Larval Toxocariasis
Lee, Che Yu
Toxocariasis and toxoplasmosis are two of the most common zoonotic parasites of people worldwide, causing ocular and neurological disease. The probability of being infected with both pathogens is increased due to shared modes of transmission. These parasites behave the same way in all paratenic hosts, which include mice and people, and so mice represent an excellent model for investigating human infection. During secondary infection of mice with Toxocara canis, many larvae become trapped in the host's liver, preventing onward migration to other body tissues such as the eye. This dissertation aimed to elucidate the immunomodulatory effect of Toxoplasma gondii infection on T. canis migratory arrest by first identifying the adaptive immune cells and humoral components contributing to trapping and then the changes elicited by co-infection. In my research, I show that CD4+ cells are critical for directing the generation of antigenspecific antibodies during primary T. canis infection, but they play no direct role in larval trapping during secondary infection. Passive immunization using purified IgG from infected mice enables naïve recipients to trap larvae in the liver, suggesting humoral immunity is the key player. I then explored the effect of concomitant infection with T. gondii on T. canis migration. Strikingly, I show that mice pre-infected with T. gondii trap far fewer larvae than mice infected only with T. canis. This corresponds to a partial shift from IgG1 antibody production to the IgG2a isotype. Reciprocal modulation by T. canis of cell-mediated immunity to T. gondii is also observed, as evidenced by a reduction in the abundance of activated CD8+ T lymphocytes in coinfected mice compared to T. gondii mono-infected mice. Finally, I examined factors with potential influence on T. canis migration. I show that male BALB/c mice have an enhanced ability to trap larvae relative to females. In contrast, no difference in larval distribution or viability is detected in eosinophil-deficient dblGATA1-/- mice on a C57BL/6 background compared to wild type. This dissertation provides insight into host immunity against larval toxocariasis and the immune cross-regulation induced by two parasites inhabiting the same host.
Toxocara; Toxoplasma; Co-infection
Simpson,Kenneth William; August,Avery; Wagner,Bettina
Ph.D. of Veterinary Medicine
Doctor of Philosophy
dissertation or thesis