Mucosal Immunity

The function of high mobility group A1 (Hmga1) chromatin remodelling proteins in intestinal stem cells (ISC) is unknown.

Background Neonatal sepsis in preterm infants is often due to organisms that colonize the skin including Staphylococcus spp. and Candida spp. Development and maturation of the skin microbiome in the neonatal period, especially in preterm infants, may be critical in preventing colonization with pathogens and subsequent progression to neonatal sepsis. Development of the skin microbiome in preterm infants or its determinants in the first 4 weeks of life has not been evaluated. Methods We evaluated the skin microbiome from three body sites, antecubital fossa, forehead and gluteal region, in a prospective cohort of 15 preterm (birth weight < 1500 g and < 32 weeks of gestation) and 15 term neonates. The microbiome community membership and relative abundance were evaluated by amplification and sequencing the bacterial V3-V5 region of the16S rRNA gene on the 454 GS FLX platform. We used linear mixed effects models to analyze longitudinal data. Results The structure and composition of the skin microbiome did not differ between the three sampling sites for term and preterm infants in the neonatal period. However, skin bacterial richness was positively associated with gestational age in the first four weeks of life. Intravenous antibiotics negatively impacted the bacterial diversity of the skin but we did not see differences with respect to feeding or mode of delivery. Conclusions Gestational age, which influences the maturity of skin structure and function, is associated with the development of the preterm cutaneous microbiome. Understanding the maturation of a healthy skin microbiome, prevention of pathogen colonization and its role in the development of immunity will be pivotal in the development of novel interventions to prevent infections in critically ill preterm infants.

Mucosal Immunology is the official publication of the Society of Mucosal Immunology (SMI). It aims to provide a forum for both basic and clinical scientists to discuss all aspects of immunity and inflammation involving mucosal tissues. The journal reflects the interests of scientists studying gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through the publication of original research articles, scholarly reviews, and timely commentaries, editorials and letters.

Vaccinations are known to protect against pathogens such as bacteria or viruses. They direct the body to form protective antibodies (IgA), and have been successfully used against some intestinal infections.

Author summary Pseudomonas aeruginosa is an opportunistic pathogen that causes life-threatening infections. P. aeruginosa disease is increasing in prevalence while bacteria continue to evolve antibiotic resistance. It is not clear how mucosal fluids usually protect against opportunistic pathogens. Knowing the key ingredients would help us understand susceptibility and develop novel biocompatible therapeutics. Mucosal fluid factors suppressing bacterial virulence may induce less bacterial resistance than traditional antimicrobials. Here we show that DMBT1, an abundant mucosal fluid glycoprotein, enabled tear fluid to inhibit P. aeruginosa twitching motility. We also show DMBT1 directly binds pili, which mediate twitching motility, suggesting a potential mechanism for twitching inhibition. Reflecting the known importance of twitching motility in virulence, purified DMBT1 reduced P. aeruginosa traversal of human cornea epithelial cell layers in vitro, and protected against P. aeruginosa induced disease in vivo, as does whole human tear fluid. These findings contribute to our understanding of mucosal fluid protection against infection, and suggest that DMBT1, or its derivatives, have potential as novel anti-virulence agents that protect against infection.

Mucosal Immunology is the official publication of the Society of Mucosal Immunology (SMI). It aims to provide a forum for both basic and clinical scientists to discuss all aspects of immunity and inflammation involving mucosal tissues. The journal reflects the interests of scientists studying gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through the publication of original research articles, scholarly reviews, and timely commentaries, editorials and letters.

Mucosal Immunology is the official publication of the Society of Mucosal Immunology (SMI). It aims to provide a forum for both basic and clinical scientists to discuss all aspects of immunity and inflammation involving mucosal tissues. The journal reflects the interests of scientists studying gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through the publication of original research articles, scholarly reviews, and timely commentaries, editorials and letters.

Author summary Melioidosis is a common cause of community-acquired pneumonia and sepsis in Asia. The causative agent, Burkholderia pseudomallei, is listed as a potential bioterror weapon. The intestinal microbiota has been suggested to be a modulator of innate immune defenses against bacterial infections. Here we investigated in mice whether the intestinal microbiota affects the clinical course of melioidosis and vice versa. The composition of the gut microbiota changed strongly during melioidosis. Mice with a disrupted gut microbiota showed increased bacterial dissemination when compared with controls following intranasal infection with B. pseudomallei, indicating that the intestinal microbiota acts as a protective factor in host defense against melioidosis. Macrophages in microbiota-disrupted mice showed a diminished capacity to phagocytose B. pseudomallei. Further research is needed to explore whether this knowledge could be used to the advantage of patients.