| First Author | Hausmann A | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 11 | PubMed ID | 34529751 |
| Mgi Jnum | J:313615 | Mgi Id | MGI:6790120 |
| Doi | 10.1084/jem.20210862 | Citation | Hausmann A, et al. (2021) Intercrypt sentinel macrophages tune antibacterial NF-kappaB responses in gut epithelial cells via TNF. J Exp Med 218(11) |
| abstractText | Intestinal epithelial cell (IEC) NF-kappaB signaling regulates the balance between mucosal homeostasis and inflammation. It is not fully understood which signals tune this balance and how bacterial exposure elicits the process. Pure LPS induces epithelial NF-kappaB activation in vivo. However, we found that in mice, IECs do not respond directly to LPS. Instead, tissue-resident lamina propria intercrypt macrophages sense LPS via TLR4 and rapidly secrete TNF to elicit epithelial NF-kappaB signaling in their immediate neighborhood. This response pattern is relevant also during oral enteropathogen infection. The macrophage-TNF-IEC axis avoids responses to luminal microbiota LPS but enables crypt- or tissue-scale epithelial NF-kappaB responses in proportion to the microbial threat. Thereby, intercrypt macrophages fulfill important sentinel functions as first responders to Gram-negative microbes breaching the epithelial barrier. The tunability of this crypt response allows the induction of defense mechanisms at an appropriate scale according to the localization and intensity of microbial triggers. |
