CELLULAR IMMUNE-RESPONSES OF JIRDS TO EXTRACTS OF LIFE-CYCLE STAGES AND ADULT EXCRETORY-SECRETORY PRODUCTS DURING THE EARLY DEVELOPMENT OF BRUGIA-PAHANGI

The Brugia-jird model of lymphatic filariasis was used to examine the induction of cellular immune responses during the early premicrofilare mic phases of the infection. The intensity of the pulmonary granulomat ous inflammatory response (PGRN) was determined by measuring granuloma areas around Sepharose beads coated with parasite extracts which were embolized in the lungs of jirds prior to necropsy. Necropsies were pe rformed at 7, 14, 28, 56, and 150 days postinfection (DPI). These time points correspond to specific developmental changes in the life cycle . Lymphocyte blastogenesis assays were performed using cells from drai ning renal lymph nodes and splenocytes at 14 and 150 DPI. Soluble extr acts of third stage larvae (L3), fourth stage larvae (L4), adult femal es, adult males, microfilariae (MF), and excretory secretory products (ES) of males and females were used in both measurements of cellular r esponsiveness. A marked granulomatous response to parasite extracts pe aked at 7 DPI or 14 DPI followed by a gradual decrease to a hyporespon sive state at 120 DPI. The response of renal lymph node cells also was significantly elevated at 14 DPI and significantly decreased at >150 DPI. The splenocyte responses were erratic and did not follow this pat tern. Significant differences in PGRN responses to somatic extract pre parations were not seen during the early stages of the infection (7, 1 4, 28 DPI), but those to MF and L3 were significantly less at 56 and 1 20 DPI. Although PGRN responses to ES followed a similar pattern, thes e were less than those to the somatic extract. The data indicated that a rapid, intense cell-mediated inflammatory response is induced early during a primary infection and that this response is rapidly downregu lated. This downregulation begins prior to the maturation of adult par asites and microfilarial production. The early phase of the cellular r esponse appears to be compartmentalized in that this response was cons istently observed in the renal lymph nodes but not in the spleen. Solu ble protein components of the parasites responsible for these response s are likely multiple and shared by all life cycle stages. (C) 1996 Ac ademic Press, Inc.