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2015 ; 83
(4
): 1507-22
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The N terminus of type III secretion needle protein YscF from Yersinia pestis
functions to modulate innate immune responses
#MMPMID25644012
Osei-Owusu P
; Jessen Condry DL
; Toosky M
; Roughead W
; Bradley DS
; Nilles ML
Infect Immun
2015[Apr]; 83
(4
): 1507-22
PMID25644012
show ga
The type III secretion system is employed by many pathogens, including the genera
Yersinia, Shigella, Pseudomonas, and Salmonella, to deliver effector proteins
into eukaryotic cells. The injectisome needle is formed by the polymerization of
a single protein, e.g., YscF (Yersinia pestis), PscF (Pseudomonas aeruginosa),
PrgI (Salmonella enterica SPI-1), SsaG (Salmonella enterica SPI-2), or MxiH
(Shigella flexneri). In this study, we demonstrated that the N termini of some
needle proteins, particularly the N terminus of YscF from Yersinia pestis,
influences host immune responses. The N termini of several needle proteins were
truncated and tested for the ability to induce inflammatory responses in a human
monocytic cell line (THP-1 cells). Truncated needle proteins induced
proinflammatory cytokines to different magnitudes than the corresponding
wild-type proteins, except SsaG. Notably, N-terminally truncated YscF induced
significantly higher activation of NF-?B and/or AP-1 and higher induction of
proinflammatory cytokines, suggesting that a function of the N terminus of YscF
is interference with host sensing of YscF, consistent with Y. pestis
pathogenesis. To directly test the ability of the N terminus of YscF to suppress
cytokine induction, a YscF-SsaG chimera with 15 N-terminal amino acids from YscF
added to SsaG was constructed. The chimeric YscF-SsaG induced lower levels of
cytokines than wild-type SsaG. However, the addition of 15 random amino acids to
SsaG had no effect on NF-?B/AP-1 activation. These results suggest that the N
terminus of YscF can function to decrease cytokine induction, perhaps
contributing to a favorable immune environment leading to survival of Y. pestis
within the eukaryotic host.