Genetic deletion of dectin-1 does not affect the course of murine experimental colitis

<p>Abstract</p> <p>Background</p> <p>It is believed that inflammatory bowel diseases (IBD) result from an imbalance in the intestinal immune response towards the luminal microbiome. Dectin-1 is a widely expressed pattern recognition receptor that recognizes fungi and upon recognition it mediates cytokine responses and skewing of the adaptive immune system. Hence, dectin-1 may be involved in the pathogenesis of IBD.</p> <p>Methods</p> <p>We assessed the responses of dectin-1 deficient macrophages to the intestinal microbiota and determined the course of acute DSS and chronic <it>Helicobacter hepaticus </it>induced colitis in dectin-1 deficient mice.</p> <p>Results</p> <p>We show that the mouse intestinal microbiota contains fungi and the cytokine responses towards this microbiota were significantly reduced in dectin-1 deficient macrophages. However, in two different colitis models no significant differences in the course of inflammation were found in dectin-1 deficient mice compared to wild type mice.</p> <p>Conclusions</p> <p>Together our data suggest that, although at the immune cell level there is a difference in response towards the intestinal flora in dectin-1 deficient macrophages, during intestinal inflammation this response seems to be redundant since dectin-1 deficiency in mice does not affect intestinal inflammation in experimental colitis.</p

Cholinergic signalling in gut immunity

The gut immune system shares many signalling molecules and receptors with the autonomic nervous system. A good example is the vagal neurotransmitter acetylcholine (ACh), for which many immune cell types express cholinergic receptors (AChR). In the last decade the vagal nerve has emerged as an integral part of an immune regulation network via its release of ACh; a system coined "the cholinergic anti-inflammatory reflex". The perspective of cholinergic immune regulation in the gut mucosa has been widened by the recent discovery of populations of ACh producing immune cells in the spleen and other organs. As such, ACh, classically referred to as neurotransmitter, may serve a much broader function as bi-directional signalling molecule between neurons and non-neuronal cell types of the immune system. (C) 2012 Elsevier Inc. All rights reserve

Leigh's disease, a fatal finding in the common world: A case report

Leigh syndrome is a neurodegenerative mitochondrial disorder of childhood characterized by symmetrical spongiform lesions in the brain. The clinical presentation of Leigh's syndrome can vary significantly. However, in the majority of cases, it usually presents as a progressive neurological disease involving motor and cognitive development. It is common to see signs and symptoms of the midbrain and brainstem involvement. Limited data are present on the brain processes occurring in Leigh's syndrome which can be attributed to fatal respiratory failure. Raised lactate levels in the blood and/or cerebrospinal fluid are noted. Magnetic resonance imaging (MRI) findings such as necrotic, symmetrical lesions in the BG/brain stem are helpful in arriving at the diagnosis of Leigh's syndrome. It's of utmost importance to determine whether fatal respiratory failure can be predicted based on clinical characteristics and findings on MRI. In our report, we presented 3 cases from rural India, including a 2-year-old male child presenting with UMN lesion signs, a 3-month-old female infant with delayed developmental milestones with lab results suggestive of Leigh's disease, and a 12-year-old female child with epistaxis and generalized weakness. As discussed above, all 3 cases presented differently with a variety of signs and symptoms and would have gone undiagnosed without the use of brain imaging. The study concluded with the impression that while MRI is essential to the initial diagnosis of Leigh's disease, MRI alone cannot be used to predict fatal respiratory failure in patients with Leigh's disease. In any dilemma regarding diagnosis even with MRI, molecular studies remain the gold standard

Acetylcholine-producing T cells in the intestine regulate antimicrobial peptide expression and microbial diversity

The cholinergic anti-inflammatory pathway reduces systemic tumor necrosis factor (TNF) via acetylcholine-producing memory T cells in the spleen. These choline acetyltransferase (ChAT)-expressing T cells are also found in the intestine, where their function is unclear. We aimed to characterize these cells in mouse and human intestine and delineate their function. We made use of the ChAT-enhanced green fluorescent protein (eGFP) reporter mice. CD4(Cre) mice were crossed to ChAT(fl/fl) mice to achieve specific deletion of ChAT in CD4(+) T cells. We observed that the majority of ChAT-expressing T cells in the human and mouse intestine have characteristics of Th17 cells and coexpress IL17A, IL22, and RORC The generation of ChAT-expressing T cells was skewed by dendritic cells after activation of their adrenergic receptor β2 To evaluate ChAT T cell function, we generated CD4-specific ChAT-deficient mice. CD4ChAT(-/-) mice showed a reduced level of epithelial antimicrobial peptides lysozyme, defensin A, and ang4, which was associated with an enhanced bacterial diversity and richness in the small intestinal lumen in CD4ChAT(-/-) mice. We conclude that ChAT-expressing T cells in the gut are stimulated by adrenergic receptor activation on dendritic cells. ChAT-expressing T cells may function to mediate the host AMP secretion, microbial growth and expansio