Influence of resistant and susceptible genotype, IL-1, and lymphoid organ on Trichinella spiralis-induced cytokine secretion

Abstract

The relative importance of cell-mediated inflammatory responses and antibody-mediated responses in controlling parasitic helminth infection is debated. To study the relationship between these responses and resistance or susceptibility to primary Trichinella spiralis infection, we infected resistant AKR mice and susceptible B10.BR mice and analyzed the lymphokines IL-2, IFN-gamma, and IL-5 produced by their T cells as a function of time and lymphoid organ. IL-2-secretors occurred maximally between days 3 and 6 postinfection, whereas IL-5-secretors peaked between days 6 and 9. Previously, we found that IFN-gamma producers peaked before day 6, whereas IL-4 producers peaked between days 6 and 9. Most cytokine secretors were CD4+. The simultaneous development of IL-2- and IFN-gamma-secreting cells, and IL-4- and IL-5-secreting cells, suggests that the infection may be stimulating T cells to differentiate into cells capable of secreting specific cytokine sets, analogous to the postulated Th1 and Th2 subsets. In the spleen and mesenteric lymph nodes, cells from B10.BR mice secreted more IL-5 than cells from AKR mice, as we found previously for IL-4. For both strains, mesenteric lymph node cells produced more IL-5 than splenocytes. The AKR mesenteric lymph node cells produced more IL-2 than the B10.BR cells, but the reverse occurred in splenocytes. The AKR peripheral lymph node cells also secreted more IFN-gamma than the B10.BR cells, but the strains were equivalent for peritoneal exudate cell IFN-gamma production. Thus, the lymphoid organ microenvironment plays an important role in regulating cytokine-secreting cell development in this system. We also tested the possible regulatory role of IL-1. Exogenous rIL-1 alpha increased IFN-gamma secretion early but not late in mesenteric lymph node cells from both strains; this reflected an increased IFN-gamma-secreting cell frequency, not a change in IFN-gamma mRNA transcript level. Exogenous rIL-1 alpha did not consistently affect IL-2, IL-4, or IL-5 secretion. These data suggest that IL-1 alpha availability in vivo may regulate IFN-gamma-secreting cell development. In sum, early activation of IFN-gamma-secreting T cells in lymph nodes, with little subsequent activation of IL-4- and IL-5-secreting cells, distinguished the resistant from susceptible strain responses to T. spiralis infection, and IL-1 alpha and lymphoid organ environment influence IFN-gamma-secreting cell activation.