TY - JOUR
T1 - B cell production of tumor necrosis factor in response to pneumocystis murina infection in mice
AU - Opata, Michael M.
AU - Ye, Zhan
AU - Hollifield, Melissa
AU - Garvy, Beth A.
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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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U2 - 10.1128/IAI.00744-13
DO - 10.1128/IAI.00744-13
M3 - Article
C2 - 24002064
AN - SCOPUS:84886778620
SN - 0019-9567
VL - 81
SP - 4252
EP - 4260
JO - Infection and Immunity
JF - Infection and Immunity
IS - 11
ER -