Mucosal Immunity

Perspective

Review Article

Review Article

Most lab mice are kept in pristine conditions, but a few immunologists think a dose of dirt could make them a better model of human disease.

As a rich source of CD4+ T cells and macrophages, the gastrointestinal (GI) tract is a major target site for HIV infection. The interplay between GI resident macrophages and intestinal epithelial cells (IECs) constitutes an important element of GI innate immunity against pathogens. In this study, we investigated whether human IECs have the ability to produce antiviral factors that can inhibit HIV infection of macrophages. We demonstrated that IECs possess functional toll-like receptor 3 (TLR3), the activation of which resulted in induction of key IFN regulatory factors (IRF3 and IRF7), IFN-β, IFN-λ and CC chemokines (MIP-1α, MIP-1β, RANTES), the ligands of HIV entry co-receptor CCR5. In addition, TLR3-activated IECs release exosomes that contained the anti-HIV factors, including IFN stimulated genes (ISGs: ISG15, ISG56, MxB, OAS-1, GBP5, and Viperin) and HIV restriction miRNAs (miRNA-17, miRNA-20, miRNA-28, miRNA-29 family members and miRNA-125b). Importantly, treatment of macrophages with supernatant (SN) from the activated IEC cultures inhibited HIV replication. Further studies showed that IEC SN could also induce the expression of antiviral ISGs and cellular HIV restriction factors (Tetherin and APOBEC3G/3F) in HIV-infected macrophages. These findings indicated that IECs might act as an important element in GI innate immunity against HIV infection/replication.

Researchers have identified a previously unknown feature of human anatomy with implications for the function of all organs, most tissues and the mechanisms of most major diseases.

Review Article

Norovirus is highly infectious and usually causes transient, acute disease. In some individuals, norovirus persists and is associated with inflammatory bowel disorders. While investigating the cell tropism for murine norovirus, Wilen et al. discovered that a rare cell type, tuft cells, carrying the CD300lf receptor were the virus's specific target. Tuft cells proliferate in response to the type 2 cytokines interleukin-4 and interleukin-25, which thereby amplify norovirus infection. Moreover, infected tuft cells are resistant to immune clearance. This effect may explain the associated persistent disease symptoms that humans can suffer.

Science , this issue p. [204][1]

[1]: /lookup/doi/10.1126/science.aar3799

As people age, their immune systems age, too. And new research at Washington University School of Medicine in St. Louis suggests that aging immune cells increase the risk for age-related macular degeneration, a major caus

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017 Jun;161(2):164-173. doi: 10.5507/bp.2017.029. Epub 2017 Jun 5.

Wilmore et al. demonstrate a role for serum IgA in protection against polymicrobial
sepsis. Induction of protective concentrations of T cell-dependent serum IgA requires
colonization of the gut with a complex microbiota that includes bacteria in the phylum
Proteobacteria.

Breast milk is the perfect nutrition for infants, a result of millions of years of evolution. In addition to providing a source of nutrition, breast milk contains a diverse array of microbiota and myriad biologically active components that are thought to guide the infant’s developing mucosal immune system. It is believed that bacteria from the mother’s intestine may translocation to breast milk and dynamically transfer to the infant. Such interplay between mother and her infant is key to establishing a healthy infant intestinal microbiome. These intestinal bacteria protect against many respiratory and diarrhoeal illnesses, but are subject to environmental stresses such as antibiotic use. Orchestrating the development of the microbiota are the human milk oligosaccharides (HMO), the synthesis of which are partially determined by the maternal genotype. HMOs are thought to play a role in preventing pathogenic bacterial adhesion though multiple mechanisms, whilst also providing nutrition for the microbiome. Extracellular vesicles (EV), including exosomes, carry a diverse cargo, including mRNA, miRNA and cytosolic and membrane-bound proteins, and are readily detectable in human breast milk. Strongly implicated in cell-cell signalling, extracellular vesicles could therefore may play a further role in the development of the infant microbiome. This review considers the emerging role of breast milk microbiota, bioactive HMOs and EVs in the establishment of the neonatal microbiom

The intestine is continuously exposed to commensal microorganisms, food, and environmental agents and also serves as a major portal of entry for many pathogens. A critical defense mechanism against microbial invasion in the intestine is the single layer of epithelial cells that separates the gut lumen from the underlying tissues. The barrier function of the intestinal epithelium is supported by cells and soluble factors of the intestinal immune system. Chief among them are intestinal intraepithelial lymphocytes (iIELs), which are embedded in the intestinal epithelium and represent one of the single largest populations of lymphocytes in the body. Compared with lymphocytes in other parts of the body, iIELs exhibit unique phenotypic, developmental, and functional properties that reflect their key roles in maintaining the intestinal epithelial barrier. In this article, we review the biology of iIELs in supporting normal health and how their dysregulation can contribute to disease.