title: B cell production of tumor necrosis factor in response to Pneumocystis murina infection in mice.
abstract: Pneumocystis species 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 upon Pneumocystis murina infection. To determine the importance of B cell-derived TNF in the primary response to P. murina, we generated bone marrow chimeras whose B cells were unable to produce TNF. The lung P. murina burden 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 from P. murina-infected TNFKO chimeras were unable to stimulate clearance of P. murina upon 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 against P. murina infection.
authors.affiliation: Departments of Microbiology, Immunology, and Molecular Genetics.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Opata
authors.forename: Zhan
authors.initials: Z
authors.lastname: Ye
authors.forename: Melissa
authors.initials: M
authors.lastname: Hollifield
authors.forename: Beth A
authors.initials: BA
authors.lastname: Garvy
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011010:Pneumocystis / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha