Mast cell-derived TNF can exacerbate mortality during severe bacterial infections in C57BL/6-KitW-sh/W-sh mice.
We used mast cell-engrafted genetically mast cell-deficient C57BL/6-Kit(W-sh/W-sh) mice to investigate the roles of mast cells and mast cell-derived tumor necrosis factor in two models of severe bacterial infection. In these mice, we confirmed findings derived from studies of mast cell-deficient WBB6F(1)-Kit(W/W-v) mice indicating that mast cells can promote survival in cecal ligation and puncture (CLP) of moderate severity. However, we found that the beneficial role of mast cells in this setting can occur independently of mast cell-derived tumor necrosis factor. By contrast, using mast cell-engrafted C57BL/6-Kit(W-sh/W-sh) mice, we found that mast cell-derived tumor necrosis factor can increase mortality during severe CLP and can also enhance bacterial growth and hasten death after intraperitoneal inoculation of Salmonella typhimurium. In WBB6F(1)-Kit(W-sh/W-sh) mice, mast cells enhanced survival during moderately severe CLP but did not significantly change the survival observed in severe CLP. Our findings in three types of genetically mast cell-deficient mice thus support the hypothesis that, depending on the circumstances (including mouse strain background, the nature of the mutation resulting in a mast cell deficiency, and type and severity of infection), mast cells can have either no detectable effect or opposite effects on survival during bacterial infections, eg, promoting survival during moderately severe CLP associated with low mortality but, in C57BL/6-Kit(W-sh/W-sh) mice, increasing mortality during severe CLP or infection with S. typhimurium.
Piliponsky
Adrian M
AM
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.
Chen
Ching-Cheng
CC
Grimbaldeston
Michele A
MA
Burns-Guydish
Stacy M
SM
Hardy
Jonathan
J
Kalesnikoff
Janet
J
Contag
Christopher H
CH
Tsai
Mindy
M
Galli
Stephen J
SJ
D000818:Animals; D001424:Bacterial Infections / Q000235:genetics / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D018450:Disease Progression; D005260:Female; D016219:Immunotherapy, Adoptive / Q000379:methods; D008407:Mast Cells / Q000378:metabolism* / Q000637:transplantation; D051379:Mice; D020297:Mice, Congenic; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D012486:Salmonella typhimurium / Q000502:physiology; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D019009:Proto-Oncogene Proteins c-kit