B Cell Production of Tumor Necrosis Factor in Response to Pneumocystis murina Infection in Mice

Abstract

ABSTRACTPneumocystisspecies are opportunistic fungal pathogens that induce tumor necrosis factor (TNF) production by alveolar macrophages. Here we report that B cells from the draining lymph nodes as well as lung CD4+T cells are important producers of TNF uponPneumocystis murinainfection. To determine the importance of B cell-derived TNF in the primary response toP. murina, we generated bone marrow chimeras whose B cells were unable to produce TNF. The lungP. murinaburden at 10 days postinfection in TNF knockout (TNFKO) chimeras was significantly higher than that in wild-type (WT) chimeras, which corresponded to reduced numbers of activated CD4+T cells in the lungs at this early time point. Furthermore, CD4+T cells isolated fromP. murina-infected TNFKO chimeras were unable to stimulate clearance ofP. murinaupon adoptive transfer to recombinase-deficient (RAG1KO) hosts. Together, these data indicate that B cell-derived TNF plays an important function in promoting CD4+T cell expansion and production of TNF and facilitating protection againstP. murinainfection.