Enhanced sensitivity of tumor necrosis factor/lymphotoxin-alpha-deficient mice to Cryptococcus neoformans infection despite increased levels of nitrite/nitrate, interferon-gamma, and interleukin-12.
The cytokine network and infection severity were characterized during disseminated cryptococcosis in tumor necrosis factor (TNF)- and lymphotoxin (Lt)-alpha-deficient mice. On day 16, the fungus burden was higher and median survival time was reduced, as was polymorphonuclear leukocyte infiltrate in the brains of knockout mice. TNF/Lt-alpha-deficient mice had lower levels of interleukin (IL)-6 in lungs and brains, IL-1beta, and the chemokine KC in brain and spleen and of the chemokine monocyte chemoattractant protein (MCP)-1 in spleen than control animals. In contrast, higher levels of IL-6, IL-10, and MCP-1 in plasma and higher levels of IL-12, interferon (IFN)-gamma, and nitrite/nitrate were found in all compartments of TNF/Lt-alpha-deficient mice. These data confirm that TNF or Lt-alpha is a key cytokine for the anticryptococcal response and demonstrate its major role for the induction of IL-1beta, IL-6, and KC in the brain; however, its presence is not a prerequisite for IL-12, IFN-gamma, and nitrite/nitrate production.
Rayhane
N
N
Unité d'Immuno-Allergie, Institut Pasteur, Paris, France.
Lortholary
O
O
Fitting
C
C
Callebert
J
J
Huerre
M
M
Dromer
F
F
Cavaillon
J M
JM
D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D018925:Chemokines / Q000096:biosynthesis; D003453:Cryptococcosis / Q000276:immunology* / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D003455:Cryptococcus neoformans / Q000254:growth & development*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
D018925:Chemokines; D016207:Cytokines; D008233:Lymphotoxin-alpha; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma