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Infect Immun, March 1998, p. 1127-1134, Vol. 66, No. 3
Department of Microbiology and Immunology,
Wake Forest University Medical Center, Winston-Salem, North Carolina
27157
Received 29 September 1997/Returned for modification 19 November
1997/Accepted 30 December 1997
During infection of the gastrointestinal tract, salmonellae induce
cytokine production and inflammatory responses which are believed to
mediate tissue damage in the host. In a previous study, we reported
that salmonellae possess the ability to stimulate tumor necrosis factor
alpha (TNF-
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Salmonella Flagellin Induces Tumor
Necrosis Factor Alpha in a Human Promonocytic Cell Line
) accumulation in primary human monocytes, as well as in
the human promonocytic cell line U38. In this model system, cytokine
upregulation is not due to lipopolysaccharide but is mediated by a
released protein. In the present study, TnphoA transposon
mutagenesis was used to identify the TNF-
-inducing factor. A mutant
Salmonella strain which lacks the ability to induce TNF-
was isolated from a TnphoA library. Genetic analysis of
this mutant demonstrated that the hns gene has been
interrupted by transposon insertion. The hns gene product
is a DNA-binding protein that regulates the expression of a variety of
unrelated genes in salmonellae. One of the known targets of
histone-like protein H1 is flhDC, the master operon which
is absolutely required for flagellar expression. Analysis of other
nonflagellated mutant Salmonella strains revealed a
correlation between the ability to induce TNF-
and the expression of
the phase 1 filament subunit protein FliC. Complementation experiments
demonstrated that FliC is sufficient to restore the ability of
nonflagellated mutant Salmonella strains to upregulate
TNF-
, whereas the phase 2 protein FljB appears to complement to a
lesser extent. In addition, Salmonella FliC can confer the
TNF-
-inducing phenotype on Escherichia coli, which
otherwise lacks the activity. Furthermore, assembly of FliC into
complete flagellar structures may not be required for induction of
TNF-
.
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, Wake Forest University Medical Center,
Medical Center Blvd., Winston-Salem, NC 27157. Phone: (336) 716-4471. Fax: (336) 716-9928. E-mail: smizel{at}bgsm.edu.
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