By
From the Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E OW3, Canada
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
We report that chlamydiae, which are obligate intracellular bacterial pathogens, can inhibit interferon (IFN)--inducible major histocompatibility complex (MHC) class II expression.
However, the IFN-
-induced IFN regulatory factor-1 (IRF-1) and intercellular adhesion molecule 1 (ICAM-1) expression is not affected, suggesting that chlamydia may selectively target
the IFN-
signaling pathways required for MHC class II expression. Chlamydial inhibition of MHC class II expression is correlated with degradation of upstream stimulatory factor (USF)-1,
a constitutively and ubiquitously expressed transcription factor required for IFN-
induction of class II transactivator (CIITA) but not of IRF-1 and ICAM-1. CIITA is an obligate mediator
of IFN-
-inducible MHC class II expression. Thus, diminished CIITA expression as a result of
USF-1 degradation may account for the suppression of the IFN-
-inducible MHC class II in
chlamydia-infected cells. These results reveal a novel immune evasion strategy used by the intracellular bacterial pathogen chlamydia that improves our understanding of the molecular basis of pathogenesis.
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Tlymphocyte recognition of MHC-peptide complexes
on target cells is essential for mounting an antigen-specific immune attack (1), which may in turn select pathogens
able to evade immune recognition by suppressing MHC expression on the infected cells (2). Many intracellular pathogens have evolved various strategies for inhibiting MHC
molecule expression on infected cells to avoid T lymphocyte recognition. For example, to escape CD8+ T cell recognition, a variety of viruses are found to suppress surface
expression of MHC class I on the infected cells (3). To
escape CD4+ T cell recognition, pathogens may need to
inhibit the IFN--inducible MHC class II expression. This
is because IFN-
induction is often required to upregulate
MHC class II molecules on nonprofessional APCs, such as
epithelial cells, that are usually the natural targets of intracellular pathogens. It has been demonstrated that IFN-
- inducible MHC class II expression is inhibited in cells infected with various intracellular pathogens (13), which
suggests that suppression of IFN-
-inducible MHC class II
may represent an immune evasion strategy used by intracellular pathogens.
Chlamydia is an obligate intracellular bacterial pathogen
(19) and the causative agent of many important human diseases (20, 21). Although specific immune responses are
provoked after a chlamydial infection, persistent infection
often occurs (22, 23). We have recently demonstrated that
chlamydia possesses a strong antiapoptotic activity (24),
which may allow chlamydiae to escape CD8+ T cell attack.
However, CD4+ T cell-mediated immunity also plays very
important roles in controlling many intracellular pathogen
infections (25, 26). As viruses that suppress IFN--inducible MHC class II expression on the infected cells can
evade CD4+ T cell recognition (16), we hypothesize that
chlamydia may have also evolved strategies for inhibiting
IFN-
induction of MHC class II, which may partially
contribute to the persistent infection. To test this hypothesis, we evaluated the effect of chlamydial infection on IFN-
-
inducible MHC class II antigen expression. We have found
that chlamydial infection can indeed suppress IFN-
-
inducible MHC class II expression by selective disruption
of IFN-
signaling pathways. We further demonstrated that a chlamydia-dependent proteasome-like activity is responsible for the chlamydial inhibitory effect. These observations reveal a novel immune evasion strategy used by the
intracellular bacterial pathogen chlamydia.
![]() |
Materials and Methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Chlamydial Infection and IFN- Stimulation.
Flow Cytometry.
Cell samples were stained with mouse anti- HLA-DRWestern Blot Assay.
Western blot assay was carried out as we previously described (24). Rabbit antibodies were used to detect IFN-RT-PCR Assay.
Cell samples were collected for RNA extraction using the Rneasy Mini Kit from QIAGEN, Inc. 2 µg of total RNA was used for each cDNA synthesis with random primers and the 1st Strand cDNA synthesis kit from Boehringer Mannheim. Aliquots of the cDNA samples were used as a template for amplifying specific gene fragments by PCR reactions (28, 29). The primers used for amplification of DR ![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
To investigate whether chlamydia
possesses the ability to evade the IFN--induced immune recognition mechanism, we evaluated IFN-
-inducible MHC
class II antigen expression in cells with or without chlamydial
infection. IFN-
significantly upregulated HLA-DR surface
expression on uninfected cells, whereas the chlamydia- infected cells displayed a minimal level of DR, regardless of IFN-
exposure (Fig. 1 A). However, chlamydial infection
did not affect the IFN-
-induced ICAM-1 surface expression (Fig. 1 A). These observations suggest that chlamydia
selectively inhibits IFN-
-inducible DR expression rather
than preventing all IFN-
dependent signaling or generally
suppressing surface protein expression. Furthermore, the total cellular protein level of IFN-
-induced HLA-DR
was also significantly diminished in chlamydia-infected cells
as compared with uninfected cells (Fig. 1 B), suggesting that
the suppression of surface expression of HLA-DR was not
due to an alteration in intracellular trafficking. The chlamydial inhibition of IFN-
-inducible HLA-DR
was reproduced in many other human cell lines, including HeLa,
MRC-5, and 2C4 (Fig. 1 B), demonstrating that the inhibitory effect is not a cell line-specific phenomenon. To determine whether the chlamydial inhibition of HLA-DR expression occurs at the transcription or translation level, MHC
class II mRNA levels were evaluated by semiquantitative
RT-PCR. IFN-
dramatically induced the expression of
DR
, DM
, and Ip41 mRNA in the uninfected but not the
infected cells (Fig. 1 C), suggesting that chlamydial inhibition
of MHC class II occurred at the transcription level. Because
the genes encoding the MHC class II presentation-related molecules DR
, DM
, and Ip41 share similar promoter
structures and CIITA is a master regulator for the expression
of these genes (30), we hypothesize that chlamydia may inhibit CIITA function or CIITA gene expression.
|
Although CIITA is constitutively expressed in professional APCs, such as dendritic cells and B
cells, IFN- stimulation is often required for the expression
of CIITA in nonprofessional APCs, such as epithelial cells
(31). CIITA mRNA expression was induced by IFN-
in
uninfected MCF-7 cells (Fig. 2 A). However, CIITA
mRNA expression was significantly lower in chlamydia-
infected and IFN-
-treated cells (Fig. 2 A), in accord with
chlamydial inhibition of MHC class II gene expression. To
investigate how CIITA gene expression was inhibited, we
measured mRNA levels for three transcription factors,
USF-1, STAT1, and IRF-1, all of which are required for
IFN-
-inducible transcription of the CIITA gene (32).
Both USF-1 and STAT1 mRNAs were constitutively expressed, and IRF-1 mRNA was induced by IFN-
in
MCF-7 cells regardless of chlamydial infection (Fig. 2 A),
suggesting that chlamydial infection did not affect transcription of the genes for these nuclear factors. Because the
three transcription factors are considered to be sufficient
and necessary for the IFN-
induction of CIITA (32), we
evaluated the protein levels of these transcription factors as
well as upstream molecules in the IFN-
signaling pathway. We found that IFN-
R, JAK-1, and STAT1 protein
levels were not altered by chlamydial infection (Fig. 2 B).
Chlamydia did not affect IFN-
-induced STAT1 tyrosine
phosphorylation (Fig. 2 B). Furthermore, IFN-
induced
both IRF-1 and ICAM-1 expression in chlamydia-infected
cells (Figs. 1 A and 2 B). As STAT1 is required for the expression of both IRF-1 and ICAM-1 genes (32, 33), we
conclude that STAT1 is transcriptionally functional in
chlamydia-infected cells. The IFN-
-induced IRF-1 in
chlamydia-infected cells may also be transcriptionally functional, as we found that IFN-
induced expression of IDO
gene in chlamydia-infected cells (data not shown), and it is
known that IRF-1 is required for IFN-
induction of IDO
(34). Therefore, the failure of the IFN-
-inducible CIITA expression in chlamydia-infected cells is likely due to the
deficiency in USF-1. We found that the USF-1 protein
was not detectable in chlamydia-infected cells (Fig. 2 B),
despite normal USF-1 mRNA expression (Fig. 2 A). We
next determined the cause of the USF-1 protein loss.
|
Because USF-1 mRNA is expressed in
chlamydia-infected cells with or without IFN- stimulation, the lack of USF-1 protein may be due to either the
inhibition of translation of USF-1 mRNA or the accelerated degradation of USF-1 protein. We tested the protein degradation hypothesis by using protease inhibitors. We
found that the proteasome inhibitor lactacystin prevented
USF-1 protein degradation in chlamydia-infected cells
(Fig. 2 C). Furthermore, the lactacystin treatment also preserved the IFN-
-inducible HLA-DR expression in chlamydia-infected cells (Fig. 2 C). These observations not only
demonstrate that a proteasome-like activity is responsible for the loss of USF-1 protein in chlamydia-infected cells
but also suggest that USF-1 degradation may be responsible
for the chlamydial suppression of MHC class II expression.
To examine whether the USF-1
protein degradation in chlamydia-infected cells is dependent on chlamydial growth and protein synthesis, we first
evaluated the relationship between the chlamydial infection
dose and USF-1 degradation. As MOI (ratio of number of
organisms versus number of host cells) increased, more
chlamydial protein was produced and less USF-1 protein
was detected (Fig. 3 A). This effect was selective, as USF-2
was not degraded, regardless of the infection dose (Fig. 3 A).
The time course relationship between chlamydial growth
and USF-1 degradation was also analyzed (Fig. 3 B). Although the STAT1 protein level was not affected by chlamydial infection at any time points examined, significant USF-1
degradation was detected 17 h after chlamydial infection, when chlamydial protein synthesis approached its maximum (Fig. 3 B). The role of chlamydial and host protein
synthesis in USF-1 degradation was examined using antibiotics specifically inhibiting either prokaryotic or eukaryotic
protein synthesis. We found that both rifampin (inhibiting
prokaryotic transcription) and chloramphenicol (inhibiting
prokaryotic translation) blocked chlamydial protein synthesis (Fig. 3 C). More importantly, these antibiotics also prevented USF-1 degradation and preserved HLA-DR expression in chlamydia-infected cells (Fig. 3 C). However,
treatment with penicillin failed to prevent USF-1 degradation and preserve HLA-DR
expression (Fig. 3 C). Penicillin only blocks chlamydial particle assembly without inhibiting chlamydial protein synthesis (35). Penicillin did not
alter the constitutively expressed USF-1 protein level and
IFN-
-inducible HLA-DR
expression in uninfected cells
(Fig. 3 C). Together, these observations demonstrate that
chlamydial protein synthesis, but not particle assembly, is
necessary for chlamydia-induced degradation of USF-1
protein and suppression of HLA-DR
expression. Finally,
cycloheximide treatment did not affect the chlamydia-
induced degradation of USF-1 (Fig. 3 C). Because cycloheximide did not affect chlamydial protein synthesis but completely inhibited new protein synthesis by the host cell, for
example, production of IFN-
-induced HLA-DR
(Fig.
3 C), we conclude that newly synthesized host proteins are
not required for chlamydia-induced degradation of USF-1.
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
We have demonstrated that the obligate intracellular
bacterial pathogen chlamydia can inhibit IFN--inducible
MHC class II expression. This inhibitory effect has also
been found with other intracellular pathogens, including
leishmania (13), listeria (14), cowdria (15), and cytomegalovirus (16). CD4+ T cell-mediated immunity plays an
important role in host defense against various intracellular
infections (36). Recognition of the infected cells by
CD4+ T cells often requires IFN-
induction of MHC
class II expression, because many pathogen-targeted cells,
such as epithelial cells, are generally MHC class II-negative. Suppression of IFN-
-inducible MHC class II expression may represent an efficient immune evasion strategy
used by intracellular pathogens to escape host defenses. Thus, chlamydial inhibition of IFN-
-inducible MHC
class II may contribute to the persistent infection caused by
chlamydia in humans (22).
It has been demonstrated that cytomegalovirus can prevent IFN--inducible class II expression in infected cells
by both IFN-
-mediated inhibition (17, 39) and disruption of IFN-
intracellular signaling pathways (16, 18).
However, mechanisms of IFN-
-inducible MHC class II
inhibition by many other intracellular pathogens are still
not clear (13). It was recently proposed that chlamydia may suppress IFN-
-inducible MHC class II expression by
stimulating host cells to release IFN-
(40). Here we show
that the intracellular bacterial pathogen chlamydia has
evolved a more specific mechanism for disrupting IFN-
signaling pathways and inhibiting MHC class II expression.
Chlamydia degrades USF-1, a downstream transcription factor required for IFN-
-inducible MHC class II but not
IRF-1 and ICAM-1 expression (Fig. 4). USF-1 degradation may represent an efficient means of interrupting IFN-
-
inducible MHC class II expression by chlamydia. Although
the constitutively and ubiquitously expressed USF-1 is a
member of the basic helix-loop-helix family consisting of
multiple transcription factors, including Myc and USF-2,
only USF-1 is both necessary and sufficient for binding to
the E box within the CIITA promoter IV and cooperating
with STAT1 and IRF-1 for promoting transcription of
CIITA (32). Therefore, the constitutively and ubiquitously
expressed USF-1 may serve as a convenient and efficient
target for chlamydia-induced degradation. The correlation
between the degradation of USF-1 and the suppression of
IFN-
-inducible MHC class II further confirms that USF-1
plays a critical role in IFN-
induction of MHC class II
(32). Besides its involvement in MHC class II expression,
USF-1 also participates in many other cellular activities, including promoting the transcription of fatty acid synthase
in response to insulin regulation (41), interfering with Ras
transformation (42), and transactivating the promoter of the
p53 tumor suppressor gene (43). Depletion of USF-1 may
cause inhibition of host cell lipid biosynthesis and promotion of host cell survival, both of which are likely beneficial
to the intracellular chlamydia organisms.
|
Proteolysis is an important aspect of normal cellular
physiology (44). Many viruses can take advantage of
host proteolysis for the purposes of evading host defenses
(2, 47). For example, human cytomegalovirus infection can
induce degradation of JAK-1, a critical upstream kinase required for IFN- JAK/STAT signaling pathways, to suppress IFN-
-inducible MHC class II on the infected cells
(18). Furthermore, the cytomegalovirus-induced degradation can be inhibited by the proteasome inhibitor Z-L3VS
(18, 48), suggesting that cytomegalovirus may be able to
manipulate host proteasome activity. Because USF-1 degradation by chlamydia is inhibitable by lactacystin and lactacystin is a potent proteasome inhibitor (48, 49), we propose
that chlamydia may also produce a factor(s) for manipulating
host proteasomes. Efforts to identify the chlamydial factor(s) are underway.
![]() |
Footnotes |
---|
Address correspondence to Guangming Zhong, Dept. of Medical Microbiology, University of Manitoba, 508-730 William Ave., Winnipeg, Manitoba, Canada R3E OW3. Phone: 204-789-3835; Fax: 204-789-3926; E-mail: gmzhong{at}cc.umanitoba.ca
Received for publication 16 February 1999 and in revised form 30 April 1999.
We thank Dr. Ronald N. Germain for helpful discussions and critically reading the manuscript and Drs. Peter Cresswell, George Stark, and Arnold Greenberg for providing useful reagents for this work.
This work was supported by the Medical Research Council (MRC) of Canada. G. Zhong is the recipient of an MRC scholarship.
Abbreviations used in this paper CIITA, class II transactivator; IDO, indoleamine 2,3-dioxygenase; IRF, interferon regulatory factor; JAK, Janus tyrosine kinase; MOI, multiplicity of infection; MOMP, major outer membrane protein; RT, reverse transcriptase; STAT, signal transducers and activators of transcription; USF, upstream stimulatory factor.
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1. | Germain, R.N.. 1994. MHC-dependent antigen processing and peptide presentation: providing ligands for T lymphocyte activation. Cell. 76: 287-299 [Medline]. |
2. |
Ploegh, H.L..
1998.
Viral strategies of immune evasion.
Science.
280:
248-253
|
3. | Ahn, K., A. Gruhler, B. Galocha, T.R. Jones, E.J. Wiertz, H.L. Ploegh, P.A. Peterson, Y. Yang, and K. Fruh. 1997. The ER-luminal domain of the HCMV glycoprotein US6 inhibits peptide translocation by TAP. Immunity. 6: 613-621 [Medline]. |
4. | Hengel, H., T. Flohr, G.J. Hammerling, U.H. Koszinowski, and F. Momburg. 1996. Human cytomegalovirus inhibits peptide translocation into the endoplasmic reticulum for MHC class I assembly. J. Gen. Virol. 77: 2287-2296 [Abstract]. |
5. |
Lehner, P.J.,
J.T. Karttunen,
G.W. Wilkinson, and
P. Cresswell.
1997.
The human cytomegalovirus US6 glycoprotein
inhibits transporter associated with antigen processing-dependent peptide translocation.
Proc. Natl. Acad. Sci. USA.
94:
6904-6909
|
6. | Jones, T.R., and L. Sun. 1997. Human cytomegalovirus US2 destabilizes major histocompatibility complex class I heavy chains. J. Virol. 71: 2970-2979 [Abstract]. |
7. |
Jones, T.R.,
E.J. Wiertz,
L. Sun,
K.N. Fish,
J.A. Nelson, and
H.L. Ploegh.
1996.
Human cytomegalovirus US3 impairs
transport and maturation of major histocompatibility complex class I heavy chains.
Proc. Natl. Acad. Sci. USA.
93:
11327-11333
|
8. |
Machold, R.P.,
E.J. Wiertz,
T.R. Jones, and
H.L. Ploegh.
1997.
The HCMV gene products US11 and US2 differ in
their ability to attack allelic forms of murine major histocompatibility complex (MHC) class I heavy chains.
J. Exp. Med.
185:
363-366
|
9. |
Schust, D.J.,
D. Tortorella,
J. Seebach,
C. Phan, and
H.L. Ploegh.
1998.
Trophoblast class I major histocompatibility
complex (MHC) products are resistant to rapid degradation
imposed by the human cytomegalovirus (HCMV) gene
products US2 and US11.
J. Exp. Med.
188:
497-503
|
10. | Wiertz, E.J., T.R. Jones, L. Sun, M. Bogyo, H.J. Geuze, and H.L. Ploegh. 1996. The human cytomegalovirus US11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol. Cell. 84: 769-779 [Medline]. |
11. |
Hughes, E.A.,
C. Hammond, and
P. Cresswell.
1997.
Misfolded major histocompatibility complex class I heavy chains
are translocated into the cytoplasm and degraded by the proteasome.
Proc. Natl. Acad. Sci. USA.
94:
1896-1901
|
12. | Collins, K.L., B.K. Chen, S.A. Kalams, B.D. Walker, and D. Baltimore. 1998. HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature. 391: 397-401 [Medline]. |
13. | Reiner, N.E., W. Ng, T. Ma, and W.R. McMaster. 1988. Kinetics of gamma interferon binding and induction of major histocompatibility complex class II mRNA in Leishmania- infected macrophages. Proc. Natl. Acad. Sci. USA. 85: 4330-4334 [Abstract]. |
14. | Schuller, S., S. Kugler, and W. Goebel. 1998. Suppression of major histocompatibility complex class I and class II gene expression in Listeria monocytogenes-infected murine macrophages. FEMS Immunol. Med. Microbiol. 20: 289-299 [Medline]. |
15. | Vachiery, N., I. Trap, P. Totte, D. Martinez, and A. Bensaid. 1998. Inhibition of MHC class I and class II cell surface expression on bovine endothelial cells upon infection with Cowdria ruminantium. Vet. Immunol. Immunopathol. 61: 37-48 [Medline]. |
16. |
Heise, M.T.,
M. Connick, and
H.W.T. Virgin.
1998.
Murine cytomegalovirus inhibits interferon ![]() |
17. |
Heise, M.T.,
J.L. Pollock,
A. O'Guin,
M.L. Barkon,
S. Bormley, and
H.W.T. Virgin.
1998.
Murine cytomegalovirus infection inhibits IFN-![]() |
18. |
Miller, D.M.,
B.M. Rahill,
J.M. Boss,
M.D. Lairmore,
J.E. Durbin,
J.W. Waldman, and
D.D. Sedmak.
1998.
Human
cytomegalovirus inhibits major histocompatibility complex
class II expression by disruption of the Jak/Stat pathway.
J.
Exp. Med.
187:
675-683
|
19. | Moulder, J.W.. 1991. Interaction of chlamydiae and host cells in vitro. Microbiol. Rev 55: 143-190 . |
20. | Grayston, J.T., C.C. Kuo, L.A. Campbell, S.P. Wang, and L.A. Jackson. 1997. Chlamydia pneumoniae and cardiovascular disease. Cardiologia. 42: 1145-1151 [Medline]. |
21. | Grayston, J.T., and S. Wang. 1975. New knowledge of chlamydiae and the diseases they cause. J. Infect. Dis. 132: 87-105 [Medline]. |
22. | Beatty, W.L., R.P. Morrison, and G.I. Byrne. 1994. Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis. Microbiol. Rev. 58: 686-699 [Abstract]. |
23. | Holland, M.J., R.L. Bailey, D.J. Conway, F. Culley, G. Miranpuri, G.I. Byrne, H.C. Whittle, and D.C. Mabey. 1996. T helper type-1 (Th1)/Th2 profiles of peripheral blood mononuclear cells (PBMC); responses to antigens of Chlamydia trachomatis in subjects with severe trachomatous scarring. Clin. Exp. Immunol. 105: 429-435 [Medline]. |
24. |
Fan, T.,
H. Lu,
H. Hu,
L. Shi,
G.A. McClarty,
D.M. Nance,
A.H. Greenberg, and
G. Zhong.
1998.
Inhibition of apoptosis in chlamydia-infected cells: blockade of mitochondrial cytochrome c release and caspase activation.
J. Exp. Med.
187:
487-496
|
25. |
Geginat, G.,
M. Lalic,
M. Kretschmar,
W. Goebel,
H. Hof,
D. Palm, and
A. Bubert.
1998.
Th1 cells specific for a secreted protein of Listeria monocytogenes are protective in vivo.
J. Immunol.
160:
6046-6055
|
26. |
Perry, L.L.,
K. Feilzer, and
H.D. Caldwell.
1997.
Immunity
to Chlamydia trachomatis is mediated by T helper 1 cells through
IFN-![]() |
27. |
Arunachalam, B.,
M. Pan, and
P. Cresswell.
1998.
Intracellular formation and cell surface expression of a complex of an
intact lysosomal protein and MHC class II molecules.
J. Immunol.
160:
5797-5806
|
28. | Chang, C.H., J.D. Fontes, M. Peterlin, and R.A. Flavell. 1994. Class II transactivator (CIITA) is sufficient for the inducible expression of major histocompatibility complex class II genes. J. Exp. Med. 180: 1367-1374 [Abstract]. |
29. |
Albanesi, C.,
A. Cavani, and
G. Girolomoni.
1998.
Interferon-![]() |
30. | Mach, B., V. Steimle, E. Martinez-Soria, and W. Reith. 1996. Regulation of MHC class II genes: lessons from a disease. Annu. Rev. Immunol. 14: 301-331 [Medline]. |
31. |
Muhlethaler-Mottet, A.,
L.A. Otten,
V. Steimle, and
B. Mach.
1997.
Expression of MHC class II molecules in different cellular and functional compartments is controlled by differential usage of multiple promoters of the transactivator
CIITA.
EMBO (Eur. Mol. Biol. Organ.) J.
16:
2851-2860
|
32. |
Muhlethaler-Mottet, A.,
W. Di Berardino,
L.A. Otten, and
B. Mach.
1998.
Activation of the MHC class II transactivator
CIITA by interferon-![]() |
33. |
Walter, M.J.,
D.C. Look,
R.M. Tidwell,
W.T. Roswit, and
M.J. Holtzman.
1997.
Targeted inhibition of interferon-![]() |
34. | Chon, S.Y., H.H. Hassanain, R. Pine, and S.L. Gupta. 1995. Involvement of two regulatory elements in interferon-gamma-regulated expression of human indoleamine 2,3- dioxygenase gene. J. Interferon Cytokine Res. 15: 517-526 [Medline]. |
35. | Barbour, A.G., K. Amano, T. Hackstadt, L. Perry, and H.D. Caldwell. 1982. Chlamydia trachomatis has penicillin-binding proteins but not detectable muramic acid. J. Bacteriol. 151: 420-428 [Medline]. |
36. | Rakhmilevich, A.L.. 1994. Evidence for a significant role of CD4+ T cells in adoptive immunity to Listeria monocytogenes in the liver. Immunology. 82: 249-254 [Medline]. |
37. | Kaufmann, S.H.. 1993. Immunity to intracellular bacteria. Annu. Rev. Immunol. 11: 129-163 [Medline]. |
38. |
Su, H.,
R. Messer,
W. Whitmire,
E. Fischer,
J.C. Portis, and
H.D. Caldwell.
1998.
Vaccination against chlamydial genital
tract infection after immunization with dendritic cells pulsed
ex vivo with nonviable Chlamydiae.
J. Exp. Med.
188:
809-818
|
39. |
Sedmak, D.D.,
S. Chaiwiriyakul,
D.A. Knight, and
W.J. Waldmann.
1995.
The role of interferon ![]() |
40. |
Rodel, J.,
A. Groh,
H. Vogelsang,
M. Lehmann,
M. Hartmann, and
E. Straube.
1998.
Beta interferon is produced by
Chlamydia trachomatis-infected fibroblast-like synoviocytes
and inhibits gamma interferon-induced HLA-DR expression.
Infect. Immun.
66:
4491-4495
|
41. |
Wang, D., and
S.H. Sul.
1997.
Upstream stimulatory factor
binding to the E-box at ![]() |
42. | Aperlo, C., E.K. Boulukos, and P. Pognonec. 1996. The basic region/helix-loop-helix/leucine repeat transcription factor USF interferes with Ras transformation. Eur. J. Biochem 241: 249-253 [Abstract]. |
43. | Reisman, D., and V. Rotter. 1993. The helix-loop-helix containing transcription factor USF binds to and transactivates the promoter of the p53 tumor suppressor gene. Nucleic Acids Res 21: 345-350 [Abstract]. |
44. | Lupas, A., J.M. Flanagan, T. Tamura, and W. Baumeister. 1997. Self-compartmentalizing proteases. Trends Biochem. Sci. 22: 399-404 [Medline]. |
45. | Glas, R., M. Bogyo, J.S. McMaster, M. Gaczynska, and H.L. Ploegh. 1998. A proteolytic system that compensates for loss of proteasome function. Nature. 392: 618-622 [Medline]. |
46. | Gottesman, S., M.R. Maurizi, and S. Wickner. 1997. Regulatory subunits of energy-dependent proteases. Cell. 91: 435-438 [Medline]. |
47. | Ploegh, H.L.. 1997. Destruction of proteins as a creative force. Immunol. Today. 18: 269-271 [Medline]. |
48. | Bogyo, M., S. Shin, J.S. McMaster, and H.L. Ploegh. 1998. Substrate binding and sequence preference of the proteasome revealed by active-site-directed affinity probes. Chem. Biol. 5: 307-320 . [Medline] |
49. | Groll, M., L. Ditzel, J. Lowe, D. Stock, M. Bochtler, H.D. Bartunik, and R. Huber. 1997. Structure of 20S proteasome from yeast at 2.4 A resolution. Nature. 386: 463-471 [Medline]. |