Mucosal Immunity

The last decade has been somewhat of a renaissance period for the field of macrophage biology. This renewed interest, combined with the advent of new technologies and development of novel model systems to assess different facets of macrophage biology, has led to major advances in our understanding...

Chromatin architecture and epigenetic regulation provide additional layers of transcriptional control (79). The transcriptional repressor B lymphocyte–induced maturation protein-1 [BLIMP-1 (PRDM1)] was among the first known inhibitors of IFNB1 expression (80). BLIMP-1 binds to the positive regulatory domain I (PRDI) sequence of the IFNB1 enhanceosome and prevents the recruitment of IRFs. Sequence analysis of the human IFNλ1 promoter region identified PRDI sequences targeted by BLIMP-1 to inhibit IFNλ1 expression in human airway and colon epithelial cells (76, 81). Similarly, loss of BLIMP-1 expression leads to an increase in IFNλ2/3 expression in murine mammary epithelial cells (76, 82). The IFNλ1 promoter was also shown to encode an E-box response element. The transcriptional repressor zinc finger E-box–binding homeobox 1 (ZEB1) bound to the IFNλ1 promoter and inhibited IFNλ1 expression (76). ZEB1 did not appear to regulate the expression of IFNB1 mRNA following treatment with the synthetic dsRNA ligand, poly(I:C). This finding was among the first to suggest a targeted mechanism for subverting the induction of an IFN-λ response. However, ZEB1 can also indirectly silence type I and III IFN signaling in diseased epithelia. During severe asthmatic disease, injury of the airway epithelium elicits TGF-β–dependent responses to promote repair of the mucosal barrier. TGF-β induces the epigenetic reprogramming of epithelial cells, leading to increases in ZEB1 expression (83). Heightened ZEB1 expression muted the accumulation of IRF1, a positive regulator of type I and III IFN gene expression (84, 85), after poly(I:C) treatment. The loss of IRF1 expression impaired antiviral responses in cells that have undergone epithelial–mesenchymal transition, making them more susceptible to respiratory syncytial virus and rhinovirus infections. Therefore, heightened ZEB1 expression could account for the imbalance in IFN responses that worsen asthmatic and allergic disease and render individuals more susceptible to viral respiratory infections (reviewed in Ref. 86). Interestingly, it is suggested that the biased induction of IFNλ1 downstream of peroxisomal-MAVS signaling is due to greater IRF1 induction (35). Whether this corresponds to a differential displacement of ZEB1 from IRF1 and/or IFNλ1 promoters remains to be addressed.

A recent paper in the journal Frontiers in Immunology describes the demonstration of mucosal antibodies in breast milk that specifically target the virus.

BackgroundLimited data are available regarding the balance of risks and benefits from human milk and/or breastfeeding during and following maternal infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).ObjectiveTo investigate whether SARS-CoV-2 can be detected in milk and on...

This study was conducted to evaluate the mucosal immune responses of rainbow trout when supplementing an experimental formulated feed with multi-strain yeast fraction product (Saccharomyces cerevisiae and Cyberlindnera jardinii).

The composition of the intestinal microbiota is associated with both the development of tumors and the efficacy of anti-tumor immunity.Here, we exami…...

While the gut and lungs are both mucosa-lined luminal organs with a shared embryological origin, their gross and micro-anatomical features are quite distinct, yielding marked differences in the composition and population dynamics of their microbiota. In the absence of vomiting or esophageal reflux, migration of microbes in the digestive tract is unidirectional (from the mouth to the anus), and is serially interrupted by widely varying physical and chemical barriers. In order for an orally introduced microbe to immigrate into the cecum, it must endure the acidic pH of the stomach (~2.0) and the alkaline pH of the duodenum (~8.0) and compete for resources with a densely populated resident microbiome. By contrast, movement of air, mucus, and microbes in the lung is bidirectional, with no physical barrier between the larynx and the most distal alveolus. Thus the microbiome of the lungs is more dynamic and transient than that of the lower gastrointestinal tract. While the gastrointestinal tract is of uniform temperature (37°C) throughout its entire 9 meters of length, the mucosa of the respiratory tract (a short half-meter in length) represents a gradient from ambient temperature at the point of inhalation to core body temperature in the alveoli [8]. Unlike the gut, the lung environment is oxygen-rich. Though the trachea and bronchi are, like the gut, lined with the heavily glycosylated proteins of secreted mucus, the vast majority of the lung’s surface area is lined with lipid-rich surfactant, which has bacteriostatic effects against select bacterial species [9]. Bacterial density in the airways is quite modest, comparable to that of the duodenum [7], orders of magnitude less than that of the large intestine; thus inter-bacterial metabolic interactions are markedly different. Finally, the gut and lungs differ in the character of host–bacterial interactions. Luminal IgA levels are far higher in the gut, while the lungs exhibit far more extraluminal interactions between bacteria and host leukocytes (alveolar macrophages). Together, these markedly divergent environmental conditions result in correspondingly divergent microbial communities.

Meconium is present in the intestines of infants before and after birth and constitutes their first bowel movements postnatally. The consistency, composition and microbial load of meconium is large...

Abstract The nose is the initial site of viral infection, replication, and transmission in the human body. Nasally inhaled vaccines may act as a promising alternative for COVID-19 management in add...

COVID-19 mRNA vaccines are highly effective at preventing COVID-19. Prior studies have found detectable SARS-CoV-2 IgG antibodies in oral mucosal specimens of participants with history of COVID-19. To assess the development of oral SARS-CoV-2 IgG antibodies among people who received either the...

Objectives: The physiological number and distribution of mast cells (MCs) in the pediatric gastro...