The iRhom2/ADAM17 Axis Attenuates Bacterial Uptake by Phagocytes in a Cell Autonomous Manner

0539726 - ÚMG 2021 RIV CH eng J - Článek v odborném periodiku
Seifert, A. - Wozniak, J. - Duesterhoeft, S. - Kašpárek, Petr - Sedláček, Radislav - Dreschers, S. - Orlikowsky, T.W. - Yildiz, D. - Ludwig, A.
The iRhom2/ADAM17 Axis Attenuates Bacterial Uptake by Phagocytes in a Cell Autonomous Manner.
International Journal of Molecular Sciences. Roč. 21, č. 17 (2020), č. článku 5978. E-ISSN 1422-0067
Grant CEP: GA MŠMT(CZ) LM2015040; GA MŠMT(CZ) LM2018126; GA MŠMT ED2.1.00/19.0395
Institucionální podpora: RVO:68378050
Klíčová slova: necrosis-factor-alpha * mycobacterium-tuberculosis * adam17 deficiency * tnf-alpha * disintegrin * inflammation * neutrophils * activation * receptor * irhom2 * metalloproteinase * adam17 * iRhom2 * bacterial phagocytosis * inflammation * infection * shedding * chemokines * phagocytes
Obor OECD: Microbiology
Impakt faktor: 5.924, rok: 2020
Způsob publikování: Open access
https://www.mdpi.com/1422-0067/21/17/5978

Uptake of bacteria by phagocytes is a crucial step in innate immune defence. Members of the disintegrin and metalloproteinase (ADAM) family critically control the immune response by limited proteolysis of surface expressed mediator molecules. Here, we investigated the significance of ADAM17 and its regulatory adapter molecule iRhom2 for bacterial uptake by phagocytes. Inhibition of metalloproteinase activity led to increased phagocytosis of pHrodo labelled Gram-negative andpositive bacteria (E. coliandS. aureus, respectively) by human and murine monocytic cell lines or primary phagocytes. Bone marrow-derived macrophages showed enhanced uptake of heat-inactivated and livingE. coliwhen they lacked either ADAM17 or iRhom2 but not upon ADAM10-deficiency. In monocytic THP-1 cells, corresponding short hairpin RNA (shRNA)-mediated knockdown confirmed that ADAM17, but not ADAM10, promoted phagocytosis ofE. coli. The augmented bacterial uptake occurred in a cell autonomous manner and was accompanied by increased release of the chemokine CXCL8, less TNF alpha release and only minimal changes in the surface expression of the receptors TNFR1, TLR6 and CD36. Inhibition experiments indicated that the enhanced bacterial phagocytosis after ADAM17 knockdown was partially dependent on TNF alpha-activity but not on CXCL8. This novel role of ADAM17 in bacterial uptake needs to be considered in the development of ADAM17 inhibitors as therapeutics.
Trvalý link: http://hdl.handle.net/11104/0317429