Vol.1, No.2, 41-49 (2011)
opyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/OJI/
Open Journal of Immunology
Dietary sugars inhibit biologic functions of the pattern
recognition molecule, mannose-binding lectin
Kazue Takahashi1, Wei-Chuan Chang1, Patience Moyo1, Mitchell R. White2, Parool Meelu3,
Anamika Verma2, Gregory L. Stahl4, Kevan L. Hartshorn2, Vijay Yajnik3*
1Program of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Bos-
ton, USA;
2Department of Medicine, Boston University School of Medicine, Boston, USA;
3Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA;
*Corresponding Author: ktakahashi1@partners.org
4Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine,
Harvard Institute of Medicine, Harvard Medical School, Boston, USA.
Received 17 August 2011; revised 1 September 2011; accepted 9 September 2011.
Mannose-binding lectin (MBL), a mammalian le-
ctin, is a pattern recognition molecule of the in-
nate immune system and recognizes carbohy-
drates that are exposed on pathogens. In this
study, we observed that fructose down regulates
MBL-mediated innate immune mechanisms ag-
ainst both influenza A Virus (IAV) and Staphylo-
coccus aureus. These mechanisms include the
lectin complement pathway and coagulation en-
zyme-like activities on both pathogens. Further-
more, fructose also reduces MBL-mediated pha-
gocytosis of S. aureus and IAV and MBL-medi-
ated IAV infection to epithelial cells. In contrast,
sucrose inhibits MBL-mediated immune mecha-
nisms agai nst S. aureus but not IAV. Together, our
studies show that dietary sugars, in particular
fructose, negatively regulate the innate immu-
nity against viral and bacterial pathogens.
Keywords: Manno s e-Binding Lectin; Fructose;
Influenza A Virus; Staphylococcus Aureus; Com-
plement; Coagulation
The innate immune system represents the first line of
host defense against pathogens. It is widely accepted that
in the lumen of our intestines, the innate immune system
is constantly interacting with the microbiota [1,2]. This
interaction is tightly regulated and is essential for both
immune tolerance and immunity against pathogens [3,4].
How our nutrition affects host-microbiome interactions
remains unknown but an increase risk of infection is
observed in patients with diabetes and obesity. These
diseases have been linked to excess consumption of
fructose and fatty foods [5,6]. Fructose, in the form of
high fructose corn syrup, along with sucrose is the main
dietary sugars in our diet [7]. How dietary sugars affect
human disease is an important question that remains
unanswered. A human study in 1973 showed that dietary
sugar intake, but not starch intake, dramatically reduced
bacterial phagocytosis [8]. Although the precise mecha-
nisms of this observation have not been understood,
these observations support the idea that dietary sugars
influence immune functions.
The innate immune system like the adaptive immune
system utilizes both cellular and humoral pathways.
Cellular defense includes epithelial cells and phagocytes,
such as macrophages and neutrophils [9]. Cell surface
receptors on innate immune cells together with soluble
lectins recognize pathogens by specific pathogen-asso-
ciated molecular patterns (PAMPs) and therefore termed
pattern recognition molecules [10]. MBL, a serum pat-
tern recognition molecule, is primarily synthesized in the
liver and in small quantity by the small intestinal epithet-
lial cells [11-14]. MBL was also identified as an opsonin
critical for bacterial (and yeast) phagocytosis [15,16]. In
addition, it is critical for defense against viruses as MBL
is identical to inhibitor found in serum and caused cal-
cium-dependent viral neutralization [17,18]. Thus, mo-
lecular patterns from virus, bacteria and yeast are recog-
nized by MBL.
Pattern recognition by MBL results in activation of
innate immune cascades. For example, MBL activates
complement via the lectin pathway, which is mediated
by MBL-associated serine protease (MASP) 1-3 [19,20].
MASPs are homologous to serum proteins C1r and C1s
K. Takahashi et al. / Open Journal of Immunology 1 (2011) 41-49
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/OJI/
that activate the classical complement pathway although
MASPs evolutionally predate C1r and C1s [21]. MBL/
MASP complex also initiates coagulation via throm-
bin-like activity [22-24]. Human MBL gene has poly-
morphisms, producing low and dysfunctional MBL,
which have been associated with increased infection
susceptibilities as reviewed [25]. Clinical observations in
human MBL deficiency were confirmed in an animal
model using MBL null mice. These mice have increased
infection susceptibility against certain pathogens and
reconstitution with exogenous MBL rescues the phenol-
type [26-29].
IAV and S. aureus are common human pathogens that
are recognized by innate immune molecules, including
MBL [30]. IAV is an RNA virus whose surface is envel-
oped with glycoproteins containing neuraminidase and
hemagglutinin, which have glycosylation sites [31]. IAV
infection could results in fatal complications, even in
individuals who are appeared to be healthy [32,33]. S.
aureus is a Gram positive bacteria present on mucosa
and skin of healthy individuals [32,34,35]. Although
normally innocuous, it may cause serious infections and
can develop severe complications leading to much high-
er morbidity and mortality [36]. This bacterial in- fection
has increased problem with rapid emergence of methicil-
lin-resistant S. aureus [37]. In addition, S. aureus can
co-infect with influenza virus resulting in increased
mortality during influenza epidemics [39].
In this study, we investigated the effects of dietary
sugars and its effect on innate immunity against common
human pathogens, IAV and S. aureus. We observed that
fructose negatively regulate MBL-mediated innate im-
mune functions against both IAV and S. aureus using
well established in vitro experimental design that reca-
pitulates environment present in the intestinal lumen and
in blood. These findings represent an important ad-
vancement in our understanding the complex interaction
between diet and human health.
2.1. Preparation of IAV and S. Aureus
Both pathogens were prepared as previously described
[28,40]. Briefly, IAV strain A/Philippine 82 (H3N2) was
grown in the chorioallantoic fluid of chicken eggs and
purified on a discontinuous sucrose gradient. Virus
stocks were dialyzed against PBS and aliquots were
stored at 80˚C. HA titers were determined by titration
with human type O, Rh- red blood cells (RBCs) in PBS.
Fluorescent foci counts (ffc) were determined by Madin-
Darby canine kidney (MDCK) cell infection assay as
previously described [41]. S. aureus was grown in Co-
lumbia media with 2% NaCl and used at mid log phase
and cfu was determined by culture on tryptic soy agar
plates [28].
2.2. MBL Binding Assay
This assay was performed using previously described
methods with a minor modification [27]. Briefly, 96 as-
say plates were coated with mannan (1 g, Sigma, MO),
IAV (1000 HA–1) or S. aureus (Reynolds CP-5+, 5 × 106 cfu)
in 50 l of a bicarbonate buffer, pH 9.5 and blocked with
BSA. The pates were added with indicated concentra-
tions of recombinant human MBL (MBL, a gift from
Enzon Pharmaceuticals. A concentration of stock was 1
mg/ml) in 50 μl and incubated at room temperature. Af-
ter rinsing, bound MBL was detected by mouse anti-
hMBL monoclonal Ab (3F8) [42] followed by alka-
line-phosphatase conjugated anti-mouse Ab (Promega,
WI) and pNTP substrate (Sigma, MO). Reaction was
read at OD 415 nm using SpectraMax M5 (Molecular
Devices, CA). For sugar inhibition experiments, indi-
cated concentrations of sugars were mixed together with
MBL at 1 μg/ml. Binding was expressed as OD415
reading. These assays were performed in triplicates and
repeated at least twice. Representative data was shown.
2.3. Mouse Sera
MBL knockout (KO) mouse sera were used to provide
MASPs [22]. Mouse sera were stored in the 80˚C freezer.
All animal experiments were performed under a protocol
approved by the Subcommittee on Research Animal Care
at Massachusetts General Hospital, Boston, MA.
2.4. Assays of the Lectin Complement
Activity and Thrombin-Like Activity
The lectin pathway assay was performed with a minor
modification of previously described method [28]. 96
well plates were prepared as in the binding assay. After
wash and blocking, wells were incubated with various
concentration of MBL with or without 1% MBL KO sera
and incubated at room temperature. After wash, the wells
were incubated with human C4 (Sigma, MO) and incu-
bated at 37˚C. After wash, the wells were incubated with
rabbit anti-hC4c Ab (Dako, CA) followed by alkaline
phosphatase-conjugated anti-rabbit Ab and then with
pNTP. The plates were read at 415 nm and the results
were expressed as U/ml. Pooled human sera with known
MBL concentration (State Sera Institute, Denmark) was
used to generate a standard curve on mannan-coated
Thrombin-like activity was performed as previously
described [22]. Briefly, 384 wells were coated as in the
binding assay. After wash, the wells were incubated with
K. Takahashi et al. / Open Journal of Immunology 1 (2011) 41-49
Copyright © 2011 SciRes. Openl y accessible at http://www.scirp.org/journal/OJI/
various concentrations of MBL with or without 1% MBL
KO sera. After wash, wells were incubated with rhoda-
mine 110-thrombin substrate R22124 (Invitrogen, CA)
in TBS-CaCl2 and read at 500 nm excitation/520 nm
emission using the SpectraMax M5. The results were
expressed as arbitrary units (AU).
For sugar inhibition on mannan, indicated concentra-
tions of various sugars were mixed with MBL 1 g/ml
with or without MBL KO sera. Sugars tested were man-
nan, N-acetyl-D-glucosamine (GlcNAc), D-fructose, and
sucrose (all sugars are from Sigma, MO). For sugar in-
hibition on IAV and S. aureus, sugars at final concentra-
tion of 10 mg/ml was mixed with MBL 1 g/ml. Inhibi-
tory activities were expressed by % inhibition that was
calculated by the formula: [(Activity by MBL) (Activ-
ity by MBL + sugars)] × 100 ÷ (Activity by MBL). In
the formula, MBL was replaced with “MBL + MBL KO
sera” for the lectin complement pathway and throm-
bin-like activity.
These assays were performed in triplicates and re-
peated at least twice and representative data was shown.
2.5. Uptake and Binding of IAV and
S. Aureus by Phagocytes
Assays were performed as previously described
[28,43,44]. Briefly, resident peritoneal macrophages of
C57B/6J (Jackson Laboratories, MI) mice were obtained
by peritoneal lavage and re-suspended in HBSS. In the
total 50 l reaction volume, 1 × 105 peritoneal macro-
phages were mixed with FITC-labeled S. aureus (FITC-
S. aureus) with MBL at 10 g/ml and with or without
fructose or galactose at 10 mg/ml. The mixture was in-
cubated on ice for 10 min and then further incu- bated
for 20 min at 37˚C.
Neutrophils from healthy volunteer donors were iso-
lated to greater than 95% purity by using dextran pre-
cipitation, followed by a Ficoll-Hypaque gradient sepa-
ration for removal of non-nuclear cells and hypotonic
lysis to eliminate contaminating erythrocytes [40]. In the
total 100 l reaction volume, 5 × 105 neutrophils were
pretreated at 37˚C for 30 min and then were further in-
cubated for 1 h at 37˚C with FITC-IAV with MBL at 10
g/ml and with or without fructose or galactose at 10
mg/ml [44].
Flow cytometry assays were performed on a FAC-
SCalibur™ (BD Biosciences) with and without addition
of 0.04% trypan blue, which quenches extracellular flu-
orescence, representing binding [28,44]. Results were
analyzed using CELLQuest™ software. Results were
expressed as % of MBL-mediated binding and uptake of
FITC-S. aureus (mean fluorescent × % total) of triplicate
2.6. IAV Neutralizing Activity Assay (Focus
This assay was performed using MDCK cells as in 2.1.
IAV was preincubated with MBL at 1 g/ml with or
without fructose at 10 mg/ml. These mixtures were in-
cubated with MDCK cells to determine IAV infection
(ffc). The assay was repeated 5 times and all data were
2.7. Statistical Anal ysis
All data were analyzed by Student t-tests to “compare
mean of each pair” using JMP software (SAS institute
Inc., NC). P values less than 0.05 was considered to be
3.1. Fructose and Sucrose Inhibit Biologic
Functions of MBL: Studies on Mannan
Mannan is an established MBL ligand derived from
yeast and in the presence of MASPs, it can activate both
complement and thrombin pathways [22]. In this study,
we used MBL KO sera as a source for MASPs and re-
combinant human MBL (Enzon Biochemicals). As sho-
wn in Figures 1(A)-(B), MBL bound to mannan and
activated the lectin complement pathway and throm-
bin-like activity, in a dose dependent manner.
We investigated effects of dietary sugars on MBL-
mannan interaction and subsequent MBL-mediated bio-
logic functions. Fructose inhibited MBL-mannan inter-
action as determined by ELISA (Figure 2(A)). Fructose
at 10 mg/ml inhibited the MBL-mannan binding by 82%,
which was greater than observed by GlcNAc, 54% (data
not shown). Furthermore, fructose inhibited the lectin
complement pathway and thrombin-like activities in a
dose dependent manner. Its inhibitory effect on biologic
function was detectable even at lower concentrations of
0.4 mg/ml and 2 mg/ml (Figure 2) and comparable to
that of mannan at a concentration of 10 mg/ml for both
the lectin complement and thrombin-like activities (Fig-
ures 2(B)-(C)).
Sucrose also inhibited these activities in a dose de-
pendent manner although it did not inhibit MBL-mannan
binding (Figure 2). Compared to fructose, the inhibitory
effect on the lectin complement pathway activity was
significantly lower, which was only 53% inhibition at a
concentration of 10 mg/ml (Figure 2(B)). In contrast,
sucrose inhibition of thrombin-like activity was over all
comparable to that of fructose and reached a plateau,
66% and 65% inhibition at 2 mg/ml and 10 mg/ml, re-
spectively (Figure 2(C)).
K. Takahashi et al. / Open Journal of Immunology 1 (2011) 41-49
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/OJI/
Figure 1. Recombinant human MBL (MBL)-
mediated functions and sugar inhibition aga-
inst mannan. (A) Binding. (B) C4 deposition.
(C) Thrombin-like activity.
Based on these experiments, fructose IC50 for binding,
the lectin complement pathway and thrombin-like activi-
ties were 22 mM, 5.5 mM and 5.5 mM, respectively,
while sucrose IC50 were > 11 mM, 2.8 mM and 2.6 mM.
In contrast to these dietary sugars, dextran, which is a
polyglucose and is similar to starch, did not inhibit
binding and the lectin complement pathway activation of
MBL on mannan even at 10 mg/ml (data not shown).
3.2. Fructose Inhibits Biologic Functions of
MBL: Studies on IAV
MBL bound to IAV in a dose dependent manner, con-
firming that MBL recognizes IAV (Figure 3(A)) [45,46].
MBL-IAV binding was inhibited by 8% and 14% by
mannan and fructose, respectively, while sucrose did not
show inhibitory effect (Figure 3(B)). To compare the ef-
fects of fructose, mannan was used as a positive control
in IAV studies. Despite the low level inhibition of
MBL-IAV binding, mannan significantly inhibited the
Figure 2. (A)-(C) Sugar inhibition assays of binding, the lectin
complement pathway, and thrombin-like activity, respectively.
Data were expressed as mean ±SEM, which were smaller than
sizes of symbols. *p < 0.0005.
lectin complement activation and thrombin-like activi-
ties, by 87% and 84% inhibition, respectively (Figures
3(C)-(D)). Accordingly, fructose (10 mg/ml) also sig-
nificantly inhibited the lectin complement and throm-
bin-like activities, by 88% and 75%, respectively (Fig-
ures 3(C)-(D)). Sucrose also showed weak inhibition on
thrombin-like activity but not on the lectin complement
activation (Figure 3(D)). Thus, fructose but not sucrose
inhibited MBL-mediated biologic functions, the lectin
complement and thrombin-like activities, by 5-fold
compared with binding inhibition.
MBL, an opsonin up regulates phagocytosis of patho-
gens. We reasoned that since fructose influences hu-
moral arm of innate immunity, it may also disrupt cellu-
lar arm as well. To study IAV uptake we designed two
experiments. First, we observed that MBL-mediated
uptake of FITC-IAV by human neutrophils was signifi-
cantly inhibited by 37% in the presence of fructose at 10
mg/ml (Figure 3(E)). However, the MBL-mediated viral
uptake was not inhibited by galactose, which is not an
MBL ligand (Figure 3(E )) [47,50]. Second, fructose also
K. Takahashi et al. / Open Journal of Immunology 1 (2011) 41-49
Copyright © 2011 SciRes. Openl y accessible at http://www.scirp.org/journal/OJI/
Figure 3. MBL-mediated functions and sugar inhibition
against IAV. (A) MBL-binding to IAV. Sugar inhibition of
binding (B), C4 deposition (C), and thrombin-like activity (D).
(E) Phagocytosis assays of FITC-IAV by human neutrophils.
Fruct and Gal indicated fructose and galactose, respectively. (F)
IAV neutralizing assay. Data were expressed as mean ± SEM,
and represent p < 0.05, p < 0.001 and p < 0.0005, respectively.
inhibited MBL’s IAV neutralization activity, which is
determined by infectivity of IAV to epithelial cells
(MDCK) as IAV infection increased when fructose was
added (Figure 3(F)). Taken together, these results dem-
onstrated that fructose down-regulated MBL-mediated
viral phagocytosis and viral neutralization.
3.3. Fructose and Sucrose Inhibit Biologic
Functions of MBL: Studies on S. Au-
Similar to against IAV, MBL bound to S. aureus, in a
dose dependent manner (Figure 4(A)). MBL-binding
was minimally inhibited only 5% - 6% by either mannan
(positive control ligand) or dietary sugars, fructose or su-
crose (Figure 4(B)). Despite the negligible-level binding
Figure 4. MBL-mediated functions and sugar inhibition
against S. aureus. (A) MBL-binding to S. aureus. Sugar inhibi-
tion assays of binding, (B) C4 deposition, (C) and throm-
bin-like activity, (D) Binding, (E) and phagocytosis, (F) assay
of FITC-S. aureus by macrophages. Fruct and Gal indicated
fructose and galactose, respectively. Data were expressed as
mean ± SEM, some of which were smaller than symbols.
*represents p < 0.0005.
inhibition, all sugars, even sucrose (all at 10 mg/ml) sig-
nificantly inhibited the lectin complement activation and
thrombin-likeactivities, in between the range of 39% -
66% and 24% - 36%, respectively (Figures 4(C)-(D)).
Once again, compared with binding inhibition, these
sugars’ inhibitory effects were 5 - 10 fold greater on the
lectin complement activation and thrombin-like active-
Regarding FITC-S. aureus binding to Regarding FIT
C-S. aureus binding to macrophages, it was signify-
cantly inhibited by 60% in the presence of fructose
(Figure 4(E)). Similarly, MBL-mediated phagocytosis
of FITC-S. aureu s was significantly inhibited by 60% in
the presence of fructose (Figure 4(F)). However, these
activeties were not inhibited by galactose, which is not
K. Takahashi et al. / Open Journal of Immunology 1 (2011) 41-49
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/OJI/
an MBL ligand (Figures 4(E)-(F)) [47,50]. Taken to-
gether, these data demonstrated that fructose negatively
regulated MBL-mediated anti-bacterial cellular functions.
Binding of pattern recognition molecules to pathogens
is a crucial step to initiate a variety of subsequent sig-
naling cascades in innate immunity, the first line of host
defense mechanisms. These mechanisms include the
lectin complement pathway activation and thrombin-like
activities [48,49]. The results of the current study dem-
onstrate that MBL initiates these activities on common
human pathogens. A highly significant and clinically
relevant finding from this study is striking inhibitory
effects by fructose and some extent by sucrose on these
innate immune functions, as we summarize our findings
in Figure 5(a).
Using functional in vitro assays, we demonstrate that
both fructose and sucrose are MBL recognition mole-
cules, and are similar to other MBL recognition mole-
cules, namely, D-mannose and GlcNAc [47,50,51]. Our
findings support recent report that fructose-lysine bound
to MBL and formed complexes with MASP [52]. These
two dietary sugars show differential kinetics in inhibi-
tion of MBL-ligand binding, suggesting that there may
be specific molecular residues that govern these interac-
tions. The importance of dietary sugar interaction with
MBL is underscored by our studies on two common pa-
thogens. Using both viral and bacterial pathogen binding
to MBL, we demonstrate that dietary sugars, specifically
fructose has a dramatic negative consequence. Mannan,
fructose and sucrose had similar low level, inhibition of
MBL binding to immobilized pathogens. However, the
biologic pathways, activation of the lectin complement
pathway and coagulation, downstream of MBL are sig-
nificantly down regulated, particularly in presence of
sucrose and fructose. Using an established bacterial and
viral phagocytosis assay we show that fructose neutral-
izes pathogen entry into phagocytes, such as macro-
phages and neutrophils, the primary cell defense in in-
nate immunity.
Differential effects of two dietary sugars were also
observed on MBL biologic function. We note that su-
crose has minimal influence on MBL-IAV (viral) inter-
actions (Figure 5(a)). This is in contrast to MBL-S.
aureus (bacterial) and MBL-mannan (fungal) interac-
tions (Figure 5(a)). It is possible that diet high in su-
crose may not affect viral innate immunity but could
influence both anti-fungal and anti-bacterial host defense.
MBL functions as an opsonin, which is a key function of
MBL-mediated anti-bacterial defense mechanism [28,53,
54]. As expected, fructose reduced MBL-mediated pha-
gocytosis of IAV and S. aureus, suggesting that fructose
reduces not only MBL-mediated humoral functions (ac-
tivation of complement and coagulation) but also
MBL-mediated cellular response. Our previous study
has demonstrated that the latter is required to reduce
bacterial growth against S. aureus [28]. On the contrary,
dextran, which is poly-glucose and is a similar to starch,
did not inhibit MBL-associated functions, such as bind-
ing and the lectin complement activation. Our finding
may partly explain the study in 1973, showing that bac-
terial phagocytosis by phagocytes isolated from healthy
volunteers was dramatically reduced by intake of dietary
sugars, including fructose, but was unaffected by starch
intake [8].
Our results also suggest that dietary sugars, in par-
ticular fructose has negative effect on innate immunity in
a dose dependent manner. Therefore, it is conceivable
that dietary sugars at low concentrations may not have
any pathological consequence. It has been observed that
in fructose fed rat, fructose concentration in the hepatic
portal vein reaches to 0.4 mg/ml, which significantly
inhibited MBL-mediated biologic functions in our study
[55]. Consumption of these dietary sugars, more so for
fructose, has skyrocketed in recent years and has been
linked to a recent increase in metabolic disease, includ-
ing diabetes and obesity [5-7]. It is also know that dia-
betic patients have increased susceptibility to infection
[6], which has been attributed to a poor circulation in
these patients. Our findings would suggest that those
dietary sugars might also be responsible by directly re-
ducing innate immune functions as blood fructose levels
reportedly increase after fructose consumption in diabe-
tes [56]. Therefore, one can speculate that intake of high
levels of dietary sugar may induce a similar situation to
MBL deficiency, which has been associated with infec-
tion susceptibility [25].
Coagulation, which is mediated by thrombin, is not
generally thought to be microbicidal, nevertheless it is a
primitive innate immune host defense mechanism, par-
ticularly in invertebrates that do not have phagocytes.
For example, tachylectins in horseshoe crab clots lipopoly-
saccharide and -glucan (PAMPs of Gram negative bacteria
and fungi, respectively), providing innate immune pro-
tection [57]. Clotting may also contain pathogen inva-
sion locally, thereby preventing systemic dissemination
of pathogen. Our recent study demonstrates that MBL
KO mice, which are susceptible to IAV and S. aureus
infection, have reduced clotting ability [22]. One can
speculate that elevated fructose in diabetic patients may
reduce local coagulation, in allowing easy pathogen es-
cape into the host. We propose that dietary sugars, in
particular high dose of fructose weakens the innate im-
mune protection, which is initiated by pattern recogni-
tion molecules, including MBL (Figure 5(b)). It is also
conceivable that pattern recognition molecules may play
K. Takahashi et al. / Open Journal of Immunology 1 (2011) 41-49
Copyright © 2011 SciRes. http://www.scirp. org/journal/OJI/
Figure 5. (a) The summary of the findings from this investigation are presented in a table form showing
the differential effects of sugar on MBL-pathogen interaction. Note: LC, the lectin complement pathway;
Coag, coagulation. Level of inhibition is presented as follows: –no effect; +/–marginal; + low; ++ in-
termediate; and +++ high. ND indicates not done. (b) The potential mechanism for the observed inhibi-
tion of innate immune mechanisms by fructose, which down regulates MBL-mediated anti-microbicidal
activities, including activation of complement, coagulation and phagocytosis. Fructose can be replaced
with sucrose, depending on its concentration and pathogen.
roles in maintaining healthy commensal microbiota by
fending off pathogenic bacteria [58,59]. In turn, the
healthy microbiota would stimulate and strengthen the
innate immune defense mechanisms. Diet can also affect
defense mechanisms. Diet can also affect microbiota
composition in mice underscoring the tight link between
diet and metabolism of intestinal bacteria [60]. Thus,
elucidating the relationships between diet, microbiota
and innate immune system will be central to our under-
standing of human health
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We would like to thank Enzon pharmaceuticals for providing MBL.
The study was in part, supported by UO1 AI074503, R21 AI077081
and 1U24AI092660. No. author has conflict of interest.
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