Abstract:
:We previously identified a cell wall-associated protein from Fusobacterium nucleatum, a Gram-negative bacterium of the oral cavity, that induces human beta defensin 2 (hBD-2) in primary human oral epithelial cells (HOECs) and designated it FAD-I (Fusobacterium-associated defensin inducer). Here, we report differential induction of hBD-2 by different strains of F. nucleatum; ATCC 25586 and ATCC 23726 induce significantly more hBD-2 mRNA than ATCC 10953. Heterologous expression of plasmid-borne fadI from the highly hBD-2-inducing strains in a ΔfadI mutant of ATCC 10953 resulted in hBD-2 induction to levels comparable to those of the highly inducing strains, indicating that FAD-I is the principal F. nucleatum agent for hBD-2 induction in HOECs. Moreover, anti-FAD-I antibodies blocked F. nucleatum induction of hBD-2 by more than 80%. Recombinant FAD-I (rFAD-I) expressed in Escherichia coli triggered levels of hBD-2 transcription and peptide release in HOECs similar to those of native FAD-I (nFAD-I) isolated from F. nucleatum ATCC 25586. Tandem mass spectrometry revealed a diacylglycerol modification at the cysteine residue in position 16 for both nFAD-I and rFAD-I. Cysteine-to-alanine substitution abrogated FAD-I's ability to induce hBD-2. Finally, FAD-I activation of hBD-2 expression was mediated via both Toll-like receptor-1/2 (TLR-1/2) and TLR-2/6 heterodimerization. Microbial molecules like FAD-I may be utilized in novel therapeutic ways to bolster the host innate immune response at mucosal surfaces.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Bhattacharyya S,Ghosh SK,Shokeen B,Eapan B,Lux R,Kiselar J,Nithianantham S,Young A,Pandiyan P,McCormick TS,Weinberg Adoi
10.1128/IAI.01311-15subject
Has Abstractpub_date
2016-04-22 00:00:00pages
1446-1456issue
5eissn
0019-9567issn
1098-5522pii
IAI.01311-15journal_volume
84pub_type
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.58.8.2535-2541.1990
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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doi:10.1128/IAI.12.5.939-942.1975
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.37.2.786-793.1982
更新日期:1982-08-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.62.7.2917-2929.1994
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:1986-03-01 00:00:00
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.61.9.3791-3802.1993
更新日期:1993-09-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.61.2.610-618.1993
更新日期:1993-02-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.59.11.3909-3916.1991
更新日期:1991-11-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.22.2.378-381.1978
更新日期:1978-11-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.62.5.1940-1945.1994
更新日期:1994-05-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.32.2.681-689.1981
更新日期:1981-05-01 00:00:00
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:1992-01-01 00:00:00
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journal_title:Infection and immunity
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更新日期:1974-04-01 00:00:00
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journal_title:Infection and immunity
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更新日期:2001-03-01 00:00:00
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journal_title:Infection and immunity
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doi:10.1128/IAI.63.11.4290-4294.1995
更新日期:1995-11-01 00:00:00
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journal_title:Infection and immunity
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更新日期:1972-10-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.67.10.5306-5314.1999
更新日期:1999-10-01 00:00:00
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journal_title:Infection and immunity
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更新日期:2015-05-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.61.4.1385-1394.1993
更新日期:1993-04-01 00:00:00