T-2 toxin impairs antifungal activities of chicken macrophages against Aspergillus fumigatus conidia but promotes the pro-inflammatory responses.
Aspergillosis is the most common fungal disease of the avian respiratory tract and is caused primarily by Aspergillus fumigatus. The respiratory macrophages provide important defence against aspergillosis. T-2 toxin (T-2), a trichothecene mycotoxin produced by Fusarium spp. in improperly stored agricultural products, has immunomodulatory effects. We studied the impact of T-2 on the antifungal response of the chicken macrophage cell line HD-11 against A. fumigatus infection. The macrophages were first exposed to 0.5 to 10 ng/ml T-2 for 24 h, and then their viability, antifungal activity, and cytokine expression in response to A. fumigatus conidial infection were determined. The viability of macrophages decreased when exposed to T-2 at concentrations higher than 1 ng/ml. One hour after conidial infection, phagocytosed conidia were observed in 30% of the non-T-2-exposed macrophages, but in only 5% of the macrophages exposed to 5 ng/ml T-2. Seven hours after infection, 24% of the conidia associated with non-T-2-exposed macrophages germinated, in contrast to 75% of those with macrophages exposed to 5 ng/ml T-2. A. fumigatus infection induced upregulation of interleukin (IL)-1β, CXCLi1, CXCLi2 and IL-12β, and downregulation of transforming growth factor-β4 in macrophages. Exposure of A. fumigatus-infected macrophages to T-2 at 1 to 5 ng/ml further upregulated the expression of IL-1β, IL-6, CCLi2, CXCLi1, CXCLi2, IL-18 (at 1 and 2 ng/ml) and IL-12β, and further downregulated that of transforming growth factor-β4 (at 5 ng/ml). In conclusion, T-2 impaired the antifungal activities of chicken macrophages against A. fumigatus conidia, but might stimulate immune response by upregulating the expression of pro-inflammatory cytokines, chemokines and T-helper 1 cytokines.
a Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine , Ghent University , Merelbeke , Belgium.
Shao-Ji
SJ
Li
Frank
F
Pasmans
Siska
S
Croubels
Elin
E
Verbrugghe
Lieven
L
Van Waeyenberghe
Zhen
Z
Yang
Freddy
F
Haesebrouck
An
A
Martel
D000818:Animals; D001228:Aspergillosis / Q000276:immunology* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000276:immunology* / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000187:drug effects / Q000378:metabolism; D002645:Chickens / Q000276:immunology*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D010587:Phagocytosis / Q000187:drug effects; D013172:Spores, Fungal; D013605:T-2 Toxin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D018925:Chemokines; D016207:Cytokines; D013605:T-2 Toxin