Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinal barrier - PubMed (original) (raw)
Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinal barrier
Matthew D Neal et al. J Immunol. 2006.
Abstract
Translocation of bacteria across the intestinal barrier is important in the pathogenesis of systemic sepsis, although the mechanisms by which bacterial translocation occurs remain largely unknown. We hypothesized that bacterial translocation across the intact barrier occurs after internalization of the bacteria by enterocytes in a process resembling phagocytosis and that TLR4 is required for this process. We now show that FcgammaRIIa-transfected enterocytes can internalize IgG-opsonized erythrocytes into actin-rich cups, confirming that these enterocytes have the molecular machinery required for phagocytosis. We further show that enterocytes can internalize Escherichia coli into phagosomes, that the bacteria remain viable intracellularly, and that TLR4 is required for this process to occur. TLR4 signaling was found to be necessary and sufficient for phagocytosis by epithelial cells, because IEC-6 intestinal epithelial cells were able to internalize LPS-coated, but not uncoated, latex particles and because MD2/TLR4-transfected human endothelial kidney (HEK)-293 cells acquired the capacity to internalize E. coli, whereas nontransfected HEK-293 cells and HEK-293 cells transfected with dominant-negative TLR4 bearing a P712H mutation did not. LPS did not induce membrane ruffling or macropinocytosis in enterocytes, excluding their role in bacterial internalization. Strikingly, the internalization of Gram-negative bacteria into enterocytes in vivo and the translocation of bacteria across the intestinal epithelium to mesenteric lymph nodes were significantly greater in wild-type mice as compared with mice having mutations in TLR4. These data suggest a novel mechanism by which bacterial translocation occurs and suggest a critical role for TLR4 in the phagocytosis of bacteria by enterocytes in this process.
Similar articles
- Toll-like receptor 4 plays a role in macrophage phagocytosis during peritoneal sepsis.
Anand RJ, Kohler JW, Cavallo JA, Li J, Dubowski T, Hackam DJ. Anand RJ, et al. J Pediatr Surg. 2007 Jun;42(6):927-32; discussion 933. doi: 10.1016/j.jpedsurg.2007.01.023. J Pediatr Surg. 2007. PMID: 17560196 - DNA attenuates enterocyte Toll-like receptor 4-mediated intestinal mucosal injury after remote trauma.
Sodhi C, Levy R, Gill R, Neal MD, Richardson W, Branca M, Russo A, Prindle T, Billiar TR, Hackam DJ. Sodhi C, et al. Am J Physiol Gastrointest Liver Physiol. 2011 May;300(5):G862-73. doi: 10.1152/ajpgi.00373.2010. Epub 2011 Jan 13. Am J Physiol Gastrointest Liver Physiol. 2011. PMID: 21233273 Free PMC article. - Nucleotide-binding oligomerization domain-2 inhibits toll-like receptor-4 signaling in the intestinal epithelium.
Richardson WM, Sodhi CP, Russo A, Siggers RH, Afrazi A, Gribar SC, Neal MD, Dai S, Prindle T Jr, Branca M, Ma C, Ozolek J, Hackam DJ. Richardson WM, et al. Gastroenterology. 2010 Sep;139(3):904-17, 917.e1-6. doi: 10.1053/j.gastro.2010.05.038. Epub 2010 May 24. Gastroenterology. 2010. PMID: 20580721 Free PMC article. - The mucosal phase of Listeria infection.
Havell EA, Beretich GR Jr, Carter PB. Havell EA, et al. Immunobiology. 1999 Dec;201(2):164-77. doi: 10.1016/S0171-2985(99)80056-4. Immunobiology. 1999. PMID: 10631565 Review. - Enterocyte death and intestinal barrier maintenance in homeostasis and disease.
Vereecke L, Beyaert R, van Loo G. Vereecke L, et al. Trends Mol Med. 2011 Oct;17(10):584-93. doi: 10.1016/j.molmed.2011.05.011. Epub 2011 Jul 6. Trends Mol Med. 2011. PMID: 21741311 Review.
Cited by
- Microbiome-Stealth Regulator of Breast Homeostasis and Cancer Metastasis.
Furuta S. Furuta S. Cancers (Basel). 2024 Aug 31;16(17):3040. doi: 10.3390/cancers16173040. Cancers (Basel). 2024. PMID: 39272898 Free PMC article. Review. - Necrotizing enterocolitis: a potential protective role for intestinal alkaline phosphatase as lipopolysaccharide detoxifying enzyme.
Martins RDS, Hulscher JBF, Timmer A, Kooi EMW, Poelstra K. Martins RDS, et al. Front Pediatr. 2024 Apr 30;12:1401090. doi: 10.3389/fped.2024.1401090. eCollection 2024. Front Pediatr. 2024. PMID: 38745834 Free PMC article. - Clinical practice guidelines for nutritional assessment and monitoring of adult ICU patients in China.
Guan X, Chen D, Xu Y. Guan X, et al. J Intensive Med. 2024 Feb 2;4(2):137-159. doi: 10.1016/j.jointm.2023.12.002. eCollection 2024 Apr. J Intensive Med. 2024. PMID: 38681796 Free PMC article. - Why put yourself on a pedestal? The pathogenic role of the A/E pedestal.
Miner MV, Rauch I. Miner MV, et al. Infect Immun. 2024 Sep 10;92(9):e0048923. doi: 10.1128/iai.00489-23. Epub 2024 Apr 9. Infect Immun. 2024. PMID: 38591884 Review. - Endotoxin-induced alterations of adipose tissue function: a pathway to bovine metabolic stress.
Chirivi M, Contreras GA. Chirivi M, et al. J Anim Sci Biotechnol. 2024 Apr 6;15(1):53. doi: 10.1186/s40104-024-01013-8. J Anim Sci Biotechnol. 2024. PMID: 38581064 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous