Date of Award

1996

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Veterinary Medical Sciences - Pathobiological Sciences

First Advisor

Thomas R. Klei

Abstract

The host systemic and peritoneal inflammatory responses against different stages of Brugia pahangi were compared in intraperitoneally infected-jirds. Systemic inflammatory responses were assessed by measuring the pulmonary granulomatous response to B. pahangi antigen-coated beads (PGRN). Peritoneal inflammation was characterized by enumeration of different cell types in peritoneal exudates following infection. Further, the toxoplasmacidal activity and TNF-$\alpha$-like production of peritoneal macrophages were also characterized. Infection with L3, L4, male worms, female worms, microfilariae (MF) or dead adult worms induced a rapid PGRN. This response decreased to levels of controls in jirds inoculated with living parasites at the chronic time period, indicating that viable worms are needed to downmodulate the PGRN, but MF are not required. Large numbers of female worms induced greater downmodulation of the PGRN than low numbers, and adult worm infection resulted in greater downmodulation of the PGRN than MF inoculation. These observations suggest that parasite burden is important in filarial-induced PGRN decrease. The greatest peritoneal inflammatory response was found in infections that resulted in MF production, and this response did not correspond to the level of PGRN indicating that MF act as potent inflammatory stimulus when compartmentalization occurs. Gamma radiation inhibited the development and decreased the survival of B. pahangi L3. This effect was inversely related to the radiation dose used. Downmodulation of the PGRN occurred in infections with normal L3 or L3 irradiated with 15 krads, but not in infections of L3 irradiated with more than 15 krads, supporting the importance of the adult stage in the PGRN downmodulation in absence of MF. The PGRN decrease occurred at the time period when the molt to adult worms had just occurred, suggesting that larval stages are also involved in the downregulation phenomenon. Macrophages from jirds inoculated with male or female B. pahangi were activated to kill Toxoplasma at 15 DPI coinciding with the peak of PGRN. TNF production peaked at 56 DPI and decreased markedly at 135 DPI. Absence of toxoplasmacidal activity was found in macrophages after 56 DPI corresponding to PGRN decrease. These data suggest that filaria-specific hyporesponsiveness may be associated with a downmodulation of macrophage function.* ftn*Originally published in DAI Volume 57, No. 7. Reprinted here with corrected text.

ISBN

9780591035261

Pages

154

Share

COinS