Commensal Microbes and Hair Follicle Morphogenesis Coordinately Drive Treg Migration into Neonatal Skin

Regulatory T cells (Tregs) are required to establish immune tolerance to commensal microbes. Tregs accumulate abruptly in the skin during a defined window of postnatal tissue development. However, the mechanisms mediating Treg migration to neonatal skin are unknown. Here we show that hair follicle (HF) development facilitates the accumulation of Tregs in neonatal skin and that upon skin entry these cells localize to HFs, a primary reservoir for skin commensals. Further, germ-free neonates had reduced skin Tregs indicating that commensal microbes augment Treg accumulation. We identified Ccl20 as a HF-derived, microbiota-dependent chemokine and found its receptor, Ccr6, to be preferentially expressed by Tregs in neonatal skin. The Ccl20-Ccr6 pathway mediated Treg migration in vitro and in vivo. Thus, HF morphogenesis, commensal microbe colonization, and local chemokine production work in concert to recruit Tregs into neonatal skin, thereby establishing this tissue Treg niche early in life

Filariasis in Travelers Presenting to the GeoSentinel Surveillance Network

As international travel increases, there is rising exposure to many pathogens not traditionally encountered in the resource-rich countries of the world. The GeoSentinel Surveillance Network, a global network of medicine/travel clinics, was established in 1995 to detect morbidity trends among travelers. Filarial infections (parasitic worm infections that cause, among others, onchocerciasis [river blindness], lymphatic filariasis [e.g. elephantiasis, lymphedema, hydrocele] and loiasis [African eyeworm]) comprised 0.62% (n = 271) of the 43,722 medical conditions reported to the GeoSentinel Network between 1995 and 2004. Immigrants from filarial-endemic regions comprised the group most likely to have acquired a filarial infection; sub-Saharan Africa was the region of the world where the majority of filarial infections were acquired. Long-term travel (greater than 1 month) was more likely to be associated with acquisition of one of the filarial infections than shorter-term travel

Genetically dictated change in host mucus carbohydrate landscape exerts a diet-dependent effect on the gut microbiota

We investigate how host mucus glycan composition interacts with dietary carbohydrate content to influence the composition and expressed functions of a human gut community. The humanized gnotobiotic mice mimic humans with a nonsecretor phenotype due to knockout of their α1-2 fucosyltransferase (Fut2) gene. The fecal microbiota of Fut2(-) mice that lack fucosylated host glycans show decreased alpha diversity relative to Fut2(+) mice and exhibit significant differences in community composition. A glucose-rich plant polysaccharide-deficient (PD) diet exerted a strong effect on the microbiota membership but eliminated the effect of Fut2 genotype. Additionally fecal metabolites predicted host genotype in mice on a polysaccharide-rich standard diet but not on a PD diet. A more detailed mechanistic analysis of these interactions involved colonization of gnotobiotic Fut2(+) and Fut2(-) mice with Bacteroides thetaiotaomicron, a prominent member of the human gut microbiota known to adaptively forage host mucosal glycans when dietary polysaccharides are absent. Within Fut2(-) mice, the B. thetaiotaomicron fucose catabolic pathway was markedly down-regulated, whereas BT4241-4247, an operon responsive to terminal β-galactose, the precursor that accumulates in the Fut2(-) mice, was significantly up-regulated. These changes in B. thetaiotaomicron gene expression were only evident in mice fed a PD diet, wherein B. thetaiotaomicron relies on host mucus consumption. Furthermore, up-regulation of the BT4241-4247 operon was also seen in humanized Fut2(-) mice. Together, these data demonstrate that differences in host genotype that affect the carbohydrate landscape of the distal gut interact with diet to alter the composition and function of resident microbes in a diet-dependent manner

Travel-associated illness trends and clusters, 2000-2010

Longitudinal data examining travel-associated illness patterns are lacking. To address this need and determine trends and clusters in travel-related illness, we examined data for 2000-2010, prospectively collected for 42,223 ill travelers by 18 GeoSentinel sites. The most common destinations from which ill travelers returned were sub-Saharan Africa (26%), Southeast Asia (17%), south-central Asia (15%), and South America (10%). The proportion who traveled for tourism decreased significantly, and the proportion who traveled to visit friends and relatives increased. Among travelers returning from malaria-endemic regions, the proportionate morbidity (PM) for malaria decreased; in contrast, the PM trends for enteric fever and dengue (excluding a 2002 peak) increased. Case clustering was detected for malaria (Africa 2000, 2007), dengue (Thailand 2002, India 2003), and enteric fever (Nepal 2009). This multisite longitudinal analysis highlights the utility of sentinel surveillance of travelers for contributing information on disease activity trends and an evidence base for travel medicine recommendations

Commensal Microbes and Hair Follicle Morphogenesis Coordinately Drive Treg Migration into Neonatal Skin.

Regulatory T cells (Tregs) are required to establish immune tolerance to commensal microbes. Tregs accumulate abruptly in the skin during a defined window of postnatal tissue development. However, the mechanisms mediating Treg migration to neonatal skin are unknown. Here we show that hair follicle (HF) development facilitates the accumulation of Tregs in neonatal skin and that upon skin entry these cells localize to HFs, a primary reservoir for skin commensals. Further, germ-free neonates had reduced skin Tregs indicating that commensal microbes augment Treg accumulation. We identified Ccl20 as a HF-derived, microbiota-dependent chemokine and found its receptor, Ccr6, to be preferentially expressed by Tregs in neonatal skin. The Ccl20-Ccr6 pathway mediated Treg migration in vitro and in vivo. Thus, HF morphogenesis, commensal microbe colonization, and local chemokine production work in concert to recruit Tregs into neonatal skin, thereby establishing this tissue Treg niche early in life

Trip duration by filarial infection among nonendemic visitors

<p>Trip duration by filarial infection among nonendemic visitors</p