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*
Department of Microbiology, College of Biological Sciences, and
Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine and Public Health, Ohio State University, Columbus, OH 43210
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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B-mediated pathway. The regulation of TLR gene expression,
however, has not been intensively studied. Here, we report that TLR2
mRNA was induced following infection of murine macrophages with
Mycobacterium avium. The changes in TLR2 mRNA correlated
with an increase in TLR2 surface expression. Infection with M.
avium resulted in a concomitant decrease in TLR4 mRNA. The
effect of M. avium infection on TLR2 mRNA appeared to be
mediated, in part, by TLR2 because the induction of the mRNA was
partially blocked by preincubation of the macrophages with an
anti-human TLR2 Ab. In contrast, the effect of LPS stimulation was
mediated via TLR4 because infection of macrophages from
LPSd mice, which do not express active TLR4, resulted in an
increase in TLR2 mRNA, while treatment of macrophages from these mice
with LPS failed to induce TLR2 mRNA. Several cytokines, including
TNF-
, IL-1, and GM-CSF, but not IFN-
, induced TLR2 mRNA.
M. avium infection resulted in the induction of TLR2
mRNA by macrophages from both TNFRI knockout and NF-B p50 knockout
mice. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Toll is a type I transmembrane receptor in Drosophila that
is involved in dorsal-ventral patterning in larvae and in the induction
of an antifungal response in adult flies (4, 5, 6).
Activation of the Toll receptor by its ligand Spatzle
results in the interaction and stimulation of several signaling
molecules that are homologous to proteins involved in NF-B
activation by the IL-1R in mammalian cells. Recently, Medzhitov et al.
(7) cloned a human receptor, homologous to Toll, which
participates in activation of cells during both innate and adaptive
immune responses. Ten members of the human TLR family have been
identified (8). At least some of these are involved in
mediating NF-B activation following the interaction of macrophages
with different bacterial pathogens or bacterial cell wall components
(9, 10, 11, 12). TLR4 has been shown to mediate the response of
macrophages to LPS (13, 14). The hyporesponsiveness of
C3H/HeJ mice (Lpsd) to LPS is the result of a
missense mutation in TLR4 (15, 16). TLR2 has been
implicated in the activation of NF-B following interaction of
macrophages with LPS, lipoarabinomannan (LAM), from mycobacterial
species and lipoteichoic acids from the cell walls of Gram-positive
bacteria (17, 18, 19, 20).
The purpose of this investigation was to study the regulation of TLR2
gene expression following the interaction of murine macrophages with
Mycobacterium avium. We found that infection with
mycobacteria resulted in an increase in TLR2 mRNA and in the expression
of TLR2 on the cell surface. Infection of macrophages from
Lpsd mice also resulted in an increase in
TLR2 mRNA, as did treatment of the macrophages with TNF-, IL-1,
and GM-CSF. In contrast, treatment of the cells with IFN- did not
affect TLR2 mRNA expression. The increase in TLR2 mRNA following
infection with M. avium is not mediated via the TNFRI, but
appears to be the result of stimulation through TLR2 by a pathway that
may be independent of NF-B.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Male, BALB/c, and C3H/HeN mice were purchased from Harlan
(Indianapolis, IN) and Charles River Laboratories (Wilmington, MA),
respectively. C3H/HeJ, C57BL/10SnJ, NF-B p50 knockout, and TNFRI
knockout mice were all obtained from The Jackson Laboratory (Bar
Harbor, ME). C57BL/10ScCr mice were obtained from National Institutes
of Health. Mice were housed in groups of five and given food and water
ad libitum. Six- to 8-wk-old mice were used as macrophage donors.
Reagents
Tissue culture media as well as murine rIFN- and restriction
enzymes PstI and HindIII were purchased from Life
Technologies (Gaithersburg, MD). LPS (Escherichia coli
O111:B4), cycloheximide, PGE2, and purified mouse
IgG were obtained from Sigma (St. Louis, MO). Recombinant TNF-,
IL-, and GM-CSF were purchased from Endogen (Woburn, MA).
FITC-conjugated rat anti-mouse IgG2a was obtained from PharMingen
(San Diego, CA). Douglas Golenbock (Boston University, Boston, MA)
kindly provided a mouse anti-human TLR2 mAb (8).
Gene-PAGE-denaturing gel was obtained from Amresco (Solon, OH), and
cDNA probe primers were constructed by Integrated DNA Technologies
(Coralville, IA). All reagents contain less than 0.1 EU/ml endotoxin,
as tested by using an endotoxin detection kit from Sigma (St.
Louis, MO).
Macrophages and mycobacterial preparation
Macrophages were harvested by peritoneal lavage 3–4 days following the i.p. injection of 4% sterile thioglycolate medium (Difco, Detroit, MI). The cells were washed with PBS and resuspended in complete IMDM (Life Technologies) containing 10% FBS (HyClone, Logan, UT) and 1% penicillin-streptomycin. Macrophages were purified by adding 6 x 106 cells/well in six-well culture plates and culturing the cells for 16 h at 37°C in 5% CO2 in air. Monolayers were washed with IMDM without serum to remove nonadherent cells and then infected with M. avium (ATCC 35712) at an 8:1 bacteria to macrophage ratio or stimulated with LPS for 3 h, as specified. Before use, the M. avium was grown in Middlebrook 7H9 broth cultures and aliquoted in 1-ml amounts and stored frozen at -70°C. Each vial contained 2.5 x 108 CFU, as determined by plate count on 7H11 agar plates.
RNase protection assay (RPA) for TLR2 and TLR4
Total mouse RNA was extracted using Ambion (Austin, TX) RNAqueous kit by following the manufacturer’s instructions. A total of 4–10 µg RNA was used for each RPA. Except for the template probe synthesis, all reagents used for the RPA were purchased from PharMingen and preformed as described by Chen et al. (21). The cDNA sequences for murine TLR2 and TLR 4 were obtained from the GenBank (accession AF124741 for TLR2; accession AF095353 for TLR4). The RT-PCR primers for the TLR2 are: 5'-ACAGCTACTGTGTGACTCTCCGCC-3' and 5'-GGTCTTGGTGTTCATTATCTTGCGC-3'. The primers for the TLR4 are: 5'-GACCTCAGCTTCAATGGTGC-3' and 5'-TATCAGAAATGCTACAGTGGATACC-3'. Briefly, the cDNA fragments of TLR2 and TLR4 were amplified by RT-PCR with 1 µg mouse peritoneal macrophage RNA using a RT-PCR kit from Roche (Indianapolis, IN). cDNA fragments of each gene were subcloned into a pGEM-T easy vector (Promega, Madison, WI). The plasmids were then transformed into DH5a competent E. coli, and selected for ampicillin resistance. Plasmid DNA was extracted using a miniprep kit from Roche, and orientation of TLR2 and TLR4 was confirmed by sequencing. For RPA, the plasmids containing the cDNA inserts were cut with PstI. The G3PDH RPA probe was created by cloning a 134-bp HindIII-ApaI fragment of G3PDH cDNA (nt 236–370) into a pBluescript SK(-) plasmid vector and the inserting plasmid DNA linearized with HindIII. The linearized plasmids were purified on 1.5% agarose gels and recovered by using a Geneclean kit (Bio 101, Vista, CA) and used as templates to create 32P-radiolabeled antisense RNA by in vitro transcription using T7 RNA polymerase for use as probes in the RPA.
Flow cytometry
Macrophages (1 x 106/ml) were fixed with 2% paraformaldehyde and washed, and 2 x 105 cells were resuspended in 200 µl of PBS containing 1% BSA and 0.01% sodium azide. The cells were preincubated with a 1 µg/ml of Fc block (PharMingen) before incubation with the mouse anti-human TLR2 Ab or an isotype control. The cells were washed and incubated with an FITC-labeled rat anti-mouse IgG2a. The cells were analyzed using a Coulter (Palo Alto, CA) Elite II flow cytometer. The data were analyzed using WinMD12.8 software. The percentage of cells expressing TLR2 was calculated by subtracting the percentage of cells stained with control IgG from the percentage of cells stained with specific anti-TLR2 Ab.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Infection of murine macrophages with M. avium resulted
in an increase in TLR2 mRNA (Fig. 1
). The
level of TLR2 mRNA increased within 1 h following the addition of
the bacteria and reached a maximum between 3 and 6 h after
infection. In contrast to that observed with TLR2, the level of TLR4
mRNA, which was high initially, decreased following infection with
M. avium. Identical results were observed with resident
peritoneal macrophages, except that they expressed slightly higher
endogenous levels of TLR2 mRNA (data not shown). The results in Fig. 2 show that expression of TLR2 on the
surface of macrophages correlated with the increase in mRNA; TLR2
expression increased from 10.9% to 31.9% following the addition of
M. avium. Infection of the cultures with Mycobacterium
bovis (strain bacillus Calmette-Guérin) or with
Mycobacterium tuberculosis (Erdman) led to similar results
(data not shown).
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Previously, it has been shown that LPS stimulates the activation
of NF-B via a TLR4-mediated pathway (14). The results
in Fig. 3A show that LPS
treatment also resulted in an increase in TLR2 mRNA, but TLR4 mRNA
decreased in macrophages from BALB/c mice. To further investigate the
effects of M. avium or LPS on TLR2 mRNA, we also used
macrophages from Lpsd mice. We found that the
induction of TLR2 mRNA by low doses of LPS was impaired in C3H/HeJ
(Lpsd) mice when compared with the effects of LPS
on TLR2 mRNA expression in C3H/HeN (Lpsn) mice
(Fig. 3B). High doses of LPS induced TLR2 mRNA in
macrophages from both strains of mice. In contrast, M. avium
infection resulted in the same level of TLR2 mRNA expression by
macrophages from both strains of mice (Fig. 3C). Similar
differences in the capacity of LPS and M. avium to induce
TRL2 mRNA were found using macrophages from C57BL/10SnJ,
Lpsn mice, and C57BL/10ScCr,
Lpsd mice (data not shown). Subsequently, we
found that pretreatment of the cells with an anti-TLR2 Ab blocked
the increase in TLR2 mRNA following the addition of M. avium
(Fig. 4).
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One effect of M. avium infection of macrophages is the
production of inflammatory cytokines such as IL-1 and TNF-.
Macrophages were treated with these and other cytokines, and their
effect on TLR2 mRNA was evaluated. IL-, TNF-, and GM-CSF
treatment increased TLR2 mRNA, while IFN- was without effect (Fig. 5A). The addition of IL-10
before infection with M. avium did not prevent the increase
in TLR2 mRNA. In contrast, the addition of PGE2
prevented the increase in TLR2 mRNA following infection with M.
avium (Fig. 5B).
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(22). It is possible, therefore,
that the effect of M. avium on TLR2 mRNA expression was the
result of the production of TNF-. To evaluate the role of TNF-
and M. avium, we used macrophages from TNFRI knockout mice.
The results in Fig. 6 show that TNF-
or infection with M. avium resulted in the induction of TLR2
mRNA by macrophages from +/+ C57BL/6J mice. In contrast, M.
avium infection resulted in an increase in TLR2 mRNA in
macrophages from TNFRI knockout mice, while TNF- failed to induce
TLR2 mRNA. Thus, the increase in TLR2 mRNA does not appear to be the
result of stimulation by TNF-.
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The addition of the PKC inhibitor bis-indolymaleimide, before
infection with M. avium, prevented the induction of TLR2
mRNA of macrophages (Fig. 7A).
Because TLR2 and TLR4 stimulation results in the activation of NF-B,
we also sought to determine whether M. avium infection
activated TLR2 mRNA transcription via a NF-B-dependent pathway. We
infected macrophages from NF-B p50 knockout mice. The results
presented in Fig. 7B show that M. avium infection
resulted in the induction of TLR2 mRNA in NF-B p50 knockout mice.
Furthermore, the addition of cycloheximide prevented the increase in
TLR2 mRNA. Similarly, cycloheximide also prevented the increase in TLR2
mRNA following treatment of the cells with TNF- (Fig. 7C). These results indicate that new protein synthesis is
required for the full induction of TLR2 mRNA by M. avium or
TNF-.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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B
via TLR2, but have not evaluated the effect of mycobacteria interaction
on TLR gene expression (8, 23). Our observations regarding
an increase in TLR2 mRNA and a decrease in TLR4 mRNA following
treatment of macrophages with LPS are similar to those reported by Yang
et al. (18, 24).
Both TLR2 and TLR4 have been reported to mediate the signaling for LPS
(14, 18). The experiments done with
TLR2-/- and TLR4-/-
mice have established an essential role of TLR4 in LPS signaling. TLR2
could be an LPS signal transducer in other species (17, 25). Golenbock and others (8, 26) have found that
TLR2 mediates NF-B activation following interaction of macrophages
with M. avium, M. tuberculosis, Trepenoma pallidum, and some
Gram-positive bacteria. In this study, we have shown that treatment of
macrophages from LPS-hyporesponsive C3H/HeJ and C57BL/10ScCr mice with
M. avium resulted in an increase in TLR2 mRNA, while their
response to LPS remained deficient. This suggests that TLR4 does not
play a role in regulating the expression of the TLR2 gene following
infection with M. avium. Our results indicate, however, that
TLR2 may play a significant role in regulating TLR2 gene expression
upon M. avium infection. Treatment of the cells with
anti-TLR2 Ab blocked the capacity of M. avium to induce
TLR2 mRNA. These observations are consistent with the previous studies
in which Fenton et al.(23) showed that TLR4 mediated LPS
stimulation, while TLR2 mediated signaling by LAM, although both LPS
and LAM are CD14 ligands. In addition, high doses of LPS were found to
induce TLR2 mRNA expression in Lpsd mice. This
suggests that there may be a TLR4-independent signaling pathway
responsible for the LPS responsiveness in
Lpsd mice.
We found that the induction of TLR2 mRNA following infection with
M. avium was also dependent on PKC activation. Infection of
macrophages with M. avium leads to the activation of PKC,
and PKC in turn is involved in the activation of many genes, such as
TNF-, IL-1, and IL-6 (27, 28). PKC functions by
regulating the activation of transcription factors such as NF-B,
c-Fos, and c-Jun (29, 30, 31). The observation that infection
with M. avium results in an increase in TLR2 mRNA in NF-B
p50 knockout mice suggests that NF-B p50 is less likely involved in
the induction of TLR2 following M. avium infection. Our
results do not exclude the possibility that other NF-B family
members may play a role in the induction of TLR2 mRNA. Indeed,
macrophages from the NF-B p50 knockout mice have been shown to
produce both IL-1 and TNF-, but not IL-6 following stimulation with
LPS (32). The recent observation that stimulation via TLR2
leads to the activation of mitogen-activated protein kinase pathway
suggests that other pathways may also be responsible for the increase
in TLR2 mRNA (33, 34). The demonstration that new protein
synthesis is required for the induction of TLR2 mRNA further indicates
that multiple signals, other than NF-B, may be involved in the
induction of TLR2 because initial NF-B activation does not require
de novo protein synthesis (35). The observation that both
LPS and M. avium induce TLR2 mRNA suggests that the TLR2
promoter contains sites for the binding of several transcription
factors. LPS stimulates via TLR4 and activates a NF-B-dependent
promoter, while M. avium, which stimulates via TLR2, results
in the activation of a pathway that does not depend on NF-B, but
appears to be activated via PKC.
Cytokines play an important role in regulating macrophage function
(36). IL-1, TNF-, and GM-CSF are produced by
macrophages shortly after infection with M. avium. Each of
these cytokines induced an increase in TLR2 mRNA. Surprisingly, in our
current system, IFN- did not stimulate TLR2 mRNA expression; neither
did IFN- affect TLR4 mRNA. Beutler et al. (37) reported
that IFN- stimulation could overcome the defective production of
TNF- in C3H/HeJ (Lpsd) mice challenged with
LPS. Our results suggest that IFN- alone does not alter the LPS
receptor (TLR4) expression. Macrophages also produce deactivating
factors such as PGE2 and IL-10 (38, 39). We also found that PGE2, but not
IL-10, suppressed the induction of TLR2 mRNA following the addition of
M. avium. Our observation with IL-10 is consistent with that
of Staege et al. (40), who found that IL-4, but not IL-10,
decreased human TLR2 mRNA. Although the mechanisms for the regulation
of TLR2 mRNA by proinflammatory cytokines and
PGE2 remain unclear, our data indicate that the
TLR2 gene expression is tightly regulated by autocrine factors produced
during the early stages of infection.
M. avium infection or treatment of macrophages with LPS
increases TLR2 mRNA, but decreases TLR4 mRNA. This suggests that these
receptors may act differently to protect the host from potential
pathogens. Both receptors activate cells via the same NF-B pathway.
Thus, LPS produced by Gram-negative bacteria leads to activation of
NF-B via TLR4, cellular activation, and the immediate production of
inflammatory cytokines. These cytokines result in a down-regulation of
TLR4, and at the same time increase the expression of TLR2. TLR2
appears to mediate cellular activation following exposure of
macrophages to pathogens whose virulence is less immediately
threatening to the host.
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Acknowledgments |
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Footnotes |
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2 Address correspondence and reprint requests to Dr. Bruce S. Zolling, Department of Microbiology, 484 West 12th Avenue, Ohio State University, Columbus, OH 43210.
3 Abbreviations used in this paper: TLR, Toll-like receptor; LAM, lipoarabinomannan; PKC, protein kinase C; RPA, RNase protection assay.
Received for publication May 10, 2000. Accepted for publication September 7, 2000.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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, IL-1
, IL-6). Cytokine 11:839.[Medline]
B by phosphorylation of its inhibitor IB. Nature 344:678.[Medline]
mRNA by protein kinase C signal transduction in macrophages. Immunology 86:49.[Medline]
B leads to multifocal defects in immune responses. Cell 80:321.[Medline]
B in lipopolysaccharide-stimulated macrophages. FEBS Lett. 467:160.[Medline]
B and interferon regulatory factor 1. Br. J. Pharmacol. 118:2178.[Medline]
interferon on cachectin expression by mononuclear phagocytes: reversal of the Lpsd (endotoxin resistance) phenotype. J. Exp. Med. 164:1791.This article has been cited by other articles:
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I. Sabroe, E. C. Jones, L. R. Usher, M. K. B. Whyte, and S. K. Dower Toll-Like Receptor (TLR)2 and TLR4 in Human Peripheral Blood Granulocytes: A Critical Role for Monocytes in Leukocyte Lipopolysaccharide Responses J. Immunol., May 1, 2002; 168(9): 4701 - 4710. [Abstract] [Full Text] [PDF]
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 R. van Crevel, T. H. M. Ottenhoff, and J. W. M. van der Meer Innate Immunity to Mycobacterium tuberculosis Clin. Microbiol. Rev., April 1, 2002; 15(2): 294 - 309. [Abstract] [Full Text] [PDF]
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J. A. Gutierrez-Pabello, D. N. McMurray, and L. G. Adams Upregulation of Thymosin {beta}-10 by Mycobacterium bovis Infection of Bovine Macrophages Is Associated with Apoptosis Infect. Immun., April 1, 2002; 70(4): 2121 - 2127. [Abstract] [Full Text] [PDF]
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T. Wang, W. P. Lafuse, and B. S. Zwilling NF{kappa}B and Sp1 Elements Are Necessary for Maximal Transcription of Toll-like Receptor 2 Induced by Mycobacterium avium J. Immunol., December 15, 2001; 167(12): 6924 - 6932. [Abstract] [Full Text] [PDF]
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