Intestinal Epithelial Toll-Like Receptor 4 Signaling Affects Epithelial Function and Colonic Microbiota and Promotes a Risk for Transmissible Colitis.

Evidence obtained from gene knockout studies supports the role of Toll-like receptor 4 (TLR4) in intestinal inflammation and microbiota recognition. Increased epithelial TLR4 expression is observed in patients with inflammatory bowel disease. However, little is known of the effect of increased TLR4 signaling on intestinal homeostasis. Here, we examined the effect of increased TLR4 signaling on epithelial function and microbiota by using transgenic villin-TLR4 mice that overexpress TLR4 in the intestinal epithelium. Our results revealed that villin-TLR4 mice are characterized by increases in the density of mucosa-associated bacteria and bacterial translocation. Furthermore, increased epithelial TLR4 signaling was associated with an impaired epithelial barrier, altered expression of antimicrobial peptide genes, and altered epithelial cell differentiation. The composition of the colonic luminal and mucosa-associated microbiota differed between villin-TLR4 and wild-type (WT) littermates. Interestingly, WT mice cohoused with villin-TLR4 mice displayed greater susceptibility to acute colitis than singly housed WT mice did. The results of this study suggest that epithelial TLR4 expression shapes the microbiota and affects the functional properties of the epithelium. The changes in the microbiota induced by increased epithelial TLR4 signaling are transmissible and exacerbate dextran sodium sulfate-induced colitis. Together, our findings imply that host innate immune signaling can modulate intestinal bacteria and ultimately the host's susceptibility to colitis.

Tick borne illness-Lyme disease.

Lyme disease is the most commonly reported tick-borneillness in the United States. Thecausative spirochete, Borrelia burgdorferi is transmitted by 4 species of Ixodes tick species. Over 90% of US cases occur in northeasternstates from Maine to Virginia, and in Wisconsin, Minnesota, and Michigan. Infection also takes place in northern California and Oregon. Lyme borreliosis is also diagnosed in parts of Europe, China, and Japan. The white-footed mouse is the primary animal reservoir for B. burgdorferi in the U.S. and the preferred host for nymphal and larval forms of the deer tick. Deer are hosts for the adult ticks but do not carry the spirochete. Signs and symptomsof infection occur in 3 stages; early localized, typified by erythema migrans; early disseminated with a flu-like syndrome, neurologic, and cardiac manifestations; and late, characteristically with arthritis. Although, the term 'Chronic Lyme Disease' has been assigned to many patients with a variety of unexplained symptoms, experts in the field question the validity of this diagnosis and warn against prolonged unproven antimicrobial therapies. Diagnosis relies upon clinical evaluation and is supported by serologic testing using a 2-step process which requires careful interpretation. Treatmentvaries with stage of disease, but normally includes doxycycline, amoxicillin,and ceftriaxone. Currently, no preventative vaccine is available. In some geographic areas, patients may be confected with Babesia, Ehrlichia, and Anaplasma since the same Ixodes ticks transmit these pathogens.