Host Resistance againstListeria monocytogenesIs Reciprocal during the Course of Infection in AlymphoplasticalyMutant Mice

Abstract

Thealyis a unique spontaneous autosomal recessive mutation in mice that causes a systemic defect of lymph nodes and Peyer's patches. We investigated host resistance againstListeria monocytogenesinfection in the mutant. The 50% lethal dose ofL. monocytogenesinaly/alymice was 10-fold higher than their heterozygotes, termedaly/+ mice, or their wild-type C57BL/6 mice. The bacterial growth in the spleens and livers ofaly/alymice was more efficient early in infection, and their listericidal activity of peritoneal macrophages was higher than those ofaly/+ mice. In contrast, the complete elimination of bacteria from the spleens and livers of infected mice in the late stage of infection, in which a T-cell-dependent mechanism is required, was delayed in thealy/alymice. Moreover, an acquired resistance against secondary infection withL. monocytogeneswas markedly diminished in thealy/alymice. The production of endogenous interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), which are critical in antilisterial resistance, was reduced in thealy/alymice during the infection. The production of IFN-γ, TNF-α, and interleukin-4 was also diminished in the spleen cell cultures ofaly/alymice when stimulated with heat-killedL. monocytogenesor the T-cell receptors were directly stimulated with anti-CD3-ϵ monoclonal antibody. These results suggest that acquired immunity againstL. monocytogenesinfection is attenuated inaly/alymice, and that the insufficient production of IFN-γ and TNF-α might be involved in the immunodeficiency.