Infection and Immunity · 2013 · 38 citations · 48 references
Veterinary MedicineImmunologyMicrobiologyHost-pathogen InteractionsImmunology Of Infectious DiseasesInnate ImmunityB Cell ActivationB Cell BiologyB-cell ResponsesCytokine BiologyImmune Responses To InfectionPulmonary InfectionsAlveolar Macrophage ResponseB Cell Responses To InfectionOpportunistic Fungal InfectionsPathogenesis Of Opportunistic PathogensPneumocystis InfectionPulmonary Fungal InfectionsPulmonary PathogenesisT Cell Expansion
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.
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Reciprocal regulation of polarized cytokine production by effector B and T cells
David P. Harris, Laura Haynes, Peter C. Sayles et al. · Nature Immunology · 2000 · 824 citations