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Altered patterns of toll-like receptor gene expression in cull cows infected with Mycobacterium avium subsp.
Supatsak Subharat1, Dairu Shu, Geoffrey W de Lisle
1AgResearch, Hopkirk Research Institute, Grasslands Research Centre, Private Bag 11008, Palmerston North 4442, New Zealand.
Abstract:
Johne's disease caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic enteric disease of cattle. The mechanism how MAP can co-exist in the gastro-intestinal tract despite a massive infiltration of immune cells is not known. Toll-like receptors (TLRs) are known to play an important role in both innate and acquired immune responses but it is unclear what role different TLRs play in response to MAP. In this study, 38 cull cows from herds infected with MAP were classified into four groups, based on MAP culture from gut tissues and histopathological lesion scores. The expression of TLR1, 2 and 4 mRNA from MAP antigen-stimulated mesenteric lymph node (MLN) cultures and peripheral blood mononuclear cells (PBMCs) and in the MLN and ileum tissues of these animals was determined. MAP antigen-specific expression of TLR1 in MLN and PBMC was significantly lower in the MAP-infected groups than the non-infected control group, suggesting that in MAP-infected animals there is impairment in the up-regulation of TLR1 in response to MAP antigen. TLR4 expression in MLN tissues was significantly higher in the severely infected group than the control group suggesting up-regulation of endogenous TLR4 expression at a site of MAP infection in animals severely affected with Johne's disease. A preliminary screening of TLR1, 2 and 4 in the cull cows revealed the presence of polymorphisms in TLR1 and TLR2. In summary, one mechanism how MAP may subvert the immune system is that there is an apparent lack of recognition of MAP antigens as foreign by TLR1 in MAP-infected cows.
Insights
Mycobacterium avium subsp. paratuberculosis (MAP) evades cattle immunity by downregulating Toll-like receptor 1 (TLR1) expression, hindering pathogen recognition. This impairment in TLR1 response is a key factor in Johne
Area of Science:
- Veterinary Immunology
- Bovine Infectious Diseases
- Molecular Biology
Background:
- Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic cattle enteric disease.
- The immune evasion mechanisms of MAP within the gastro-intestinal tract remain poorly understood.
- Toll-like receptors (TLRs) are crucial in innate and acquired immunity, but their specific roles in MAP infection are unclear.
Purpose of the Study:
- To investigate the expression and function of Toll-like receptors (TLRs) 1, 2, and 4 in cattle with Johne's disease.
- To determine how MAP influences TLR gene expression in immune cells and tissues.
- To explore potential polymorphisms in TLR genes associated with susceptibility to MAP infection.
Main Methods:
- Analysis of TLR1, TLR2, and TLR4 mRNA expression in mesenteric lymph node (MLN) cultures, peripheral blood mononuclear cells (PBMCs), and gut tissues from MAP-infected and control cattle.
- Stimulation of MLN and PBMC cultures with MAP antigens.
- Histopathological scoring and MAP culturing from gut tissues to classify infection severity.
- Screening for polymorphisms in TLR1, TLR2, and TLR4 genes.
Main Results:
- MAP antigen-specific TLR1 expression was significantly lower in infected cattle, indicating impaired TLR1 upregulation in response to MAP.
- TLR4 expression was significantly higher in MLN tissues of severely infected cattle, suggesting localized upregulation.
- Polymorphisms in TLR1 and TLR2 genes were detected in the studied cattle population.
Conclusions:
- Impaired recognition of MAP antigens by TLR1 may be a mechanism by which MAP evades the host immune system in infected cattle.
- Differential expression of TLR1 and TLR4 suggests complex immune responses to MAP infection.
- TLR gene polymorphisms warrant further investigation for their role in Johne's disease susceptibility.
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