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Tetanus toxin impairs accessory and secretory functions in interferon-gamma-treated murine macrophages
L Pitzurra1, C Adami, M Sevilla
1Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, 06122, Italy.
Abstract:
Tetanus neurotoxin (TT), a product of microbial origin, acts as a zinc endopeptidase on vesicle-associated membrane proteins (VAMP). We have demonstrated that TT displays inhibitory effects on secretory and accessory functions in the murine macrophage (Mphi) cell line GG2EE. Nitric oxide (NO) secretion was decreased when interferon (IFN)-gamma-pretreated GG2EE Mphis were coincubated with a fungal costimulus (SMP200) and TT. When heat-inactivated TT was used this effect was not evident. The TT-mediated phenomenon was dose-dependent and specific since, under the same experimental conditions, it did not affect interleukin-6 or tumor necrosis factor-alpha secretion. Furthermore, IFN-gamma-induced major histocompatibility complex class II molecule expression and GG2EE accessory function, assessed by SMP200-stimulated lymphoproliferation, were also inhibited by TT. Such inhibition was incomplete, in line with our previous results showing that TT partially cleaves VAMP proteins in murine Mφ.
Insights
Tetanus neurotoxin (TT) inhibits nitric oxide (NO) secretion and immune cell function in macrophages. This effect is specific and dose-dependent, highlighting TT
Area of Science:
- Immunology
- Neuroscience
- Microbiology
Background:
- Tetanus neurotoxin (TT) is a microbial zinc endopeptidase targeting vesicle-associated membrane proteins (VAMP).
- Macrophages (Mphi) play crucial roles in immune responses, including the secretion of nitric oxide (NO) and antigen presentation.
Purpose of the Study:
- To investigate the inhibitory effects of TT on secretory and accessory functions of the murine macrophage cell line GG2EE.
Main Methods:
- Co-incubation of interferon (IFN)-gamma-pretreated GG2EE Mphis with a fungal costimulus (SMP200) and TT.
- Measurement of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) secretion.
- Assessment of major histocompatibility complex class II (MHC class II) expression and Mphi accessory function (lymphoproliferation).
Main Results:
- TT significantly decreased NO secretion in IFN-gamma-stimulated GG2EE Mphis when co-incubated with SMP200; this effect was not observed with heat-inactivated TT.
- TT's inhibitory effect was dose-dependent and specific, as IL-6 and TNF-alpha secretion remained unaffected.
- TT partially inhibited IFN-gamma-induced MHC class II expression and GG2EE accessory function, correlating with previous findings of partial VAMP cleavage.
Conclusions:
- Tetanus neurotoxin exhibits inhibitory effects on key macrophage functions, including NO secretion and antigen presentation.
- The findings suggest TT's potential to modulate immune responses by targeting macrophage secretory and accessory functions.