Počet záznamů: 1
Bordetella Adenylate Cyclase Toxin Inhibits Monocyte-to-Macrophage Transition and Dedifferentiates Human Alveolar Macrophages into Monocyte-like Cells
- 1.
SYSNO ASEP 0518311 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Bordetella Adenylate Cyclase Toxin Inhibits Monocyte-to-Macrophage Transition and Dedifferentiates Human Alveolar Macrophages into Monocyte-like Cells Tvůrce(i) Ahmad, Jawid Nazir (MBU-M) RID
Holubová, Jana (MBU-M) RID, ORCID
Benada, Oldřich (MBU-M) ORCID, RID
Kofroňová, Olga (MBU-M) RID, ORCID
Stehlík, L. (CZ)
Vašáková, M. (CZ)
Šebo, Peter (MBU-M) RID, ORCIDČíslo článku e01743-19 Zdroj.dok. mBio. - : American Society for Microbiology - ISSN 2161-2129
Roč. 10, č. 5 (2019)Poč.str. 16 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova Bordetella ; adenylate cyclase toxin ; cyclic AMP Vědní obor RIV EE - Mikrobiologie, virologie Obor OECD Microbiology CEP GX19-27630X GA ČR - Grantová agentura ČR NV16-28126A GA MZd - Ministerstvo zdravotnictví EF16_013/0001818 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy LO1509 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora MBU-M - RVO:61388971 UT WOS 000493915800048 EID SCOPUS 85072615839 DOI 10.1128/mBio.01743-19 Anotace Monocytes arriving at the site of infection differentiate into functional effector macrophages to replenish the resident sentinel cells. Bordetella pertussis, the pertussis agent, secretes an adenylate cyclase toxin-hemolysin (CyaA) that binds myeloid phagocytes through complement receptor 3 (CD11b/CD18) and swiftly delivers its adenylyl cyclase enzyme domain into phagocytes. This ablates the bactericidal capacities of phagocytes through massive and unregulated conversion of cytosolic ATP into the key signaling molecule cAMP. We show that exposure of primary human monocytes to as low a concentration as 22.5 pM CyaA, or a low (2:1) multiplicity of infection by CyaA-producing B. pertussis bacteria, blocks macrophage colony-stimulating factor (M-CSF)-driven differentiation of monocytes. CyaA-induced cAMP signaling mediated through the activity of protein kinase A (PKA) efficiently blocked expression of macrophage markers, and the monocytes exposed to 22.5 pM CyaA failed to acquire the characteristic intracellular complexity of mature macrophage cells. Neither M-CSF-induced endoplasmic reticulum (ER) expansion nor accumulation of Golgi bodies, mitochondria, or lysosomes was observed in toxin-exposed monocytes, which remained small and poorly phagocytic and lacked pseudopodia. Exposure to 22.5 pM CyaA toxin provoked loss of macrophage marker expression on in vitro differentiated macrophages, as well as on primary human alveolar macrophages, which appeared to dedifferentiate into monocyte-like cells with upregulated CD14 levels. This is the first report that terminally differentiated tissue-resident macrophage cells can be dedifferentiated in vitro. The results suggest that blocking of monocyte-to-macrophage transition and/or dedifferentiation of the sentinel cells of innate immunity through cAMP-elevating toxin action may represent a novel immune evasion strategy of bacterial pathogens.
Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2020 Elektronická adresa https://mbio.asm.org/content/10/5/e01743-19
Počet záznamů: 1