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Diacylated lipopeptide from Mycoplasma synoviae mediates TLR15 induced innate immune responses
Irena Oven, Katarina Resman Rus, Daliborka Dušanić
1Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Groblje 3, SI-1230 DomŽale, Slovenia. mojca.narat@bf.uni-lj.si.
Abstract:
Avian-specific toll like receptor 15 (TLR15) is functionally equivalent to a group of TLR2 family proteins that the mammalian innate immune system utilizes to recognize a broad spectrum of microbe-associated molecular patterns, including bacterial lipoproteins. In this study we examined the role of chicken TLR2 family members in the innate immune response to the avian pathogenic bacterium, Mycoplasma synoviae. We found that Mycoplasma synoviae, and specifically the N-terminal diacylated lipopeptide (MDLP) representing the amino-terminal portion of its mature haemagglutinin protein, significantly induces the expression of TLR15, but not TLR1 and TLR2 in chicken macrophages and chondrocytes. TLR15 activation is specific and depends on diacylation of the lipopeptide. Activation of TLR15 after stimulation with Mycoplasma synoviae and MDLP triggers an increase in the expression of transcription factor nuclear factor kappa B and nitric oxide production. Moreover, transfection of avian macrophage cells with small interfering RNA reduces the expression of TLR15 after stimulation with MDLP. This leads to decreased activation of the innate immune response, as measured by nitric oxide production. Additionally, pretreatment of cells with neutralizing anti-TLR15 antibody results in a notable attenuation of MDLP-driven release of nitric oxide. This positive correlation may constitute a mechanism for stimulating the innate immune response against avian mycoplasmas in chicken cells via TLR15.
Insights
Chicken toll-like receptor 15 (TLR15) plays a key role in recognizing avian mycoplasmas. This innate immune receptor is crucial for nitric oxide production in response to Mycoplasma synoviae.
Area of Science:
- Immunology
- Avian Biology
- Microbiology
Background:
- Avian-specific toll-like receptor 15 (TLR15) is part of the innate immune system, similar to mammalian TLR2 family proteins.
- TLR2 family proteins recognize microbe-associated molecular patterns, such as bacterial lipoproteins.
Purpose of the Study:
- To investigate the role of chicken TLR2 family members in the innate immune response to Mycoplasma synoviae.
- To determine if TLR15 is involved in recognizing Mycoplasma synoviae and its components.
Main Methods:
- Chicken macrophages and chondrocytes were stimulated with Mycoplasma synoviae and its N-terminal diacylated lipopeptide (MDLP).
- Gene expression of TLR15, TLR1, and TLR2 was analyzed.
- Nuclear factor kappa B activation and nitric oxide production were measured.
- Small interfering RNA was used to reduce TLR15 expression.
- Neutralizing anti-TLR15 antibody was used to block TLR15 function.
Main Results:
- Mycoplasma synoviae and MDLP specifically induced TLR15 expression, not TLR1 or TLR2.
- TLR15 activation required diacylation of the lipopeptide.
- Stimulation led to increased nuclear factor kappa B and nitric oxide production.
- Reduced TLR15 expression decreased nitric oxide production.
- Blocking TLR15 attenuated MDLP-induced nitric oxide release.
Conclusions:
- Chicken TLR15 is a key receptor for recognizing Mycoplasma synoviae.
- TLR15 activation by diacylated lipopeptides stimulates innate immune responses, including nitric oxide production.
- TLR15 may be a crucial component in the chicken's defense against avian mycoplasmas.
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