PLoS pathogens, 2012-05, Vol.8 (5), p.e1002670-e1002670
2012
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- Autor(en) / Beteiligte
- Titel
- Age-dependent TLR3 expression of the intestinal epithelium contributes to rotavirus susceptibility
- Ist Teil von
- PLoS pathogens, 2012-05, Vol.8 (5), p.e1002670-e1002670
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Rotavirus is a major cause of diarrhea worldwide and exhibits a pronounced small intestinal epithelial cell (IEC) tropism. Both human infants and neonatal mice are highly susceptible, whereas adult individuals remain asymptomatic and shed only low numbers of viral particles. Here we investigated age-dependent mechanisms of the intestinal epithelial innate immune response to rotavirus infection in an oral mouse infection model. Expression of the innate immune receptor for viral dsRNA, Toll-like receptor (Tlr) 3 was low in the epithelium of suckling mice but strongly increased during the postnatal period inversely correlating with rotavirus susceptibility, viral shedding and histological damage. Adult mice deficient in Tlr3 (Tlr3(-/-)) or the adaptor molecule Trif (Trif(Lps2/Lps2)) exerted significantly higher viral shedding and decreased epithelial expression of proinflammatory and antiviral genes as compared to wild-type animals. In contrast, neonatal mice deficient in Tlr3 or Trif did not display impaired cell stimulation or enhanced rotavirus susceptibility. Using chimeric mice, a major contribution of the non-hematopoietic cell compartment in the Trif-mediated antiviral host response was detected in adult animals. Finally, a significant age-dependent increase of TLR3 expression was also detected in human small intestinal biopsies. Thus, upregulation of epithelial TLR3 expression during infancy might contribute to the age-dependent susceptibility to rotavirus infection.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1553-7374, 1553-7366eISSN: 1553-7374DOI: 10.1371/journal.ppat.1002670Titel-ID: cdi_plos_journals_1289079702
- Format
- –
- Schlagworte
- adaptor proteins, Adaptor Proteins, Vesicular Transport - deficiency, Adaptor Proteins, Vesicular Transport - genetics, Adaptor Proteins, Vesicular Transport - metabolism, Age, Aging, Animal models, Animals, Biology, Biopsy, Clinical Medicine, Cytogenetics, Diarrhea, Digestive tract, Disease Susceptibility, Double-stranded RNA, Epithelial cells, Epithelium, Gene expression, Genetic aspects, Health aspects, Human rotavirus, Humans, Immune response, Immune system, Infants, Infection, Inflammation, Intestinal Mucosa - immunology, Intestinal Mucosa - metabolism, Intestinal Mucosa - microbiology, Intestine, Intestine, Small - immunology, Intestine, Small - virology, Kinases, Klinisk medicin, Medical research, Medicin och hälsovetenskap, Medicine, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microorganisms, Mucosa, Neonates, Pathogens, Physiological aspects, Proteins, Receptors, Pattern Recognition - biosynthesis, Replication, Rodents, Rotavirus, Rotavirus - pathogenicity, Rotavirus Infections - immunology, Rotavirus Infections - virology, Rotaviruses, Suckling behavior, TLR3 protein, Toll-Like Receptor 3 - deficiency, Toll-Like Receptor 3 - genetics, Toll-Like Receptor 3 - metabolism, Toll-like receptors, Tropism, Viral genetics, Virulence (Microbiology), Virus Shedding