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Noora Ottman, Justus Reunanen, Marjolein Meijerink, Taija E. Pietilä, Veera Kainulainen, Judith Klievink, Laura Huuskonen, Steven Aalvink, Mikael Skurnik, Sjef Boeren, Reetta Satokari, Annick Mercenier, Airi Palva, Hauke Smidt, Willem M. de Vos, Clara Belzer
Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function
www.plosone.org
www.plosone.org
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(other)Tj
2.3187 0 Td
(commensals,)Tj
/F13 1 Tf
5.3234 0 Td
[()31()6()7()7()11()12( )14()4()6()-4()11()2()-9( )12(\n)12()]TJ
6.8372 0 Td
[(\r)11()20()16(\n)-4()10()18( )14( )12( )]TJ
/F7 1 Tf
4.371 0 Td
(A2-165)Tj
3.1237 0 Td
(and)Tj
/F13 1 Tf
1.7121 0 Td
[()-3()6()-4()11()13()4()6()1( )4()4()12(\n)-4()]TJ
5.2214 0 Td
[(\r)10()4()16()22()11()16()-9(\n)12()]TJ
/F7 1 Tf
-31.6117 -1.3039 Td
(WCFS1.)Tj
3.5149 0 Td
(A)Tj
0.8957 0 Td
(proteomics)Tj
4.6488 0 Td
(approach)Tj
3.9005 0 Td
(was)Tj
1.6781 0 Td
(used)Tj
2.0352 0 Td
(to)Tj
1.0092 0 Td
(identify)Tj
3.2428 0 Td
(candidate-signaling)Tj
7.9426 0 Td
(molecules)Tj
4.1386 0 Td
(from)Tj
2.1826 0 Td
(bacte-)Tj
-35.189 -1.2982 Td
(rial)Tj
1.5136 0 Td
(fractions,)Tj
3.8835 0 Td
(and)Tj
1.7121 0 Td
(a)Tj
0.6463 0 Td
(collection)Tj
4.0535 0 Td
(of)Tj
1.0035 0 Td
(these)Tj
2.2223 0 Td
(proteins)Tj
3.4696 0 Td
(was)Tj
1.6781 0 Td
(purified)Tj
3.3619 0 Td
(from)Tj
2.1826 0 Td
(overproducing)Tj
/F13 1 Tf
6.0548 0 Td
[()-4()-3()13()6()2()-9( )4()13()18( )4()]TJ
-31.7818 -1.2983 Td
[()7()10()12( )]TJ
/F7 1 Tf
1.525 0 Td
(clones.)Tj
2.9026 0 Td
(These)Tj
2.5285 0 Td
(proteins)Tj
3.4526 0 Td
(were)Tj
2.092 0 Td
(tested)Tj
2.5058 0 Td
(for)Tj
1.3549 0 Td
(their)Tj
2.0693 0 Td
(capacity)Tj
3.4129 0 Td
(to)Tj
1.0035 0 Td
(induce)Tj
2.8913 0 Td
(TLR2-signaling,)Tj
6.548 0 Td
(cytokine)Tj
3.5773 0 Td
(pro-)Tj
-35.8637 -1.2983 Td
(duction)Tj
3.2768 0 Td
(and)Tj
1.7121 0 Td
(to)Tj
1.0148 0 Td
(affect)Tj
2.3357 0 Td
(trans-epithelial)Tj
6.1398 0 Td
(resistance)Tj
4.0706 0 Td
(\(TEER\))Tj
3.2371 0 Td
(in)Tj
1.0261 0 Td
(Caco-2)Tj
3.0388 0 Td
(model)Tj
2.7099 0 Td
(system.)Tj
3.1237 0 Td
(Localization)Tj
5.0343 0 Td
(of)Tj
-36.7197 -1.3039 Td
(specific)Tj
3.1407 0 Td
(proteins)Tj
3.4696 0 Td
(was)Tj
1.6781 0 Td
(studied)Tj
3.1124 0 Td
(with)Tj
1.9729 0 Td
(immunofluorescence)Tj
8.5719 0 Td
(labeling)Tj
3.3052 0 Td
(using)Tj
2.3641 0 Td
(specific)Tj
3.1408 0 Td
(antibodies.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 613.5874 cm
BT
/F3 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Materials)Tj
4.5071 0 Td
(and)Tj
1.989 0 Td
(methods)Tj
/F0 1 Tf
-6.4961 -1.4976 Td
(Bacterial)Tj
4.0582 0 Td
(growth)Tj
3.1891 0 Td
(conditions)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 578.6078 cm
BT
/F13 1 Tf
1 TL
-0.004 Tc
0 0 Td
[()20()6()8()2()-9()6()16()10( )4()]TJ
5.4311 0 Td
[()18(\n)4()1( )12()18( )10(\r)10()18( )4()4()]TJ
/F7 1 Tf
4.9266 0 Td
(MucT)Tj
2.6759 0 Td
(\(ATTC)Tj
3.1294 0 Td
(BAA-835\))Tj
4.286 0 Td
(was)Tj
1.7007 0 Td
(grown)Tj
2.795 0 Td
(in)Tj
1.0374 0 Td
(a)Tj
0.652 0 Td
(basal)Tj
2.2054 0 Td
(medium)Tj
3.6056 0 Td
(as)Tj
1.0148 0 Td
(described)Tj
-33.4599 -1.2982 Td
(previously)Tj
4.3483 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(].)Tj
1.6044 0 Td
(The)Tj
1.7801 0 Td
(medium)Tj
3.6057 0 Td
(was)Tj
1.7007 0 Td
(supplemented)Tj
5.8507 0 Td
(with)Tj
2.0013 0 Td
(either)Tj
2.5284 0 Td
(hog)Tj
1.7235 0 Td
(gastric)Tj
2.8403 0 Td
(mucin)Tj
2.8063 0 Td
(\(0.5%,)Tj
2.7156 0 Td
(Type)Tj
2.228 0 Td
(III;)Tj
-35.7333 -1.3039 Td
(Sigma-Aldrich,)Tj
6.3042 0 Td
(St.)Tj
1.2189 0 Td
(Louis,)Tj
2.6475 0 Td
(MO,)Tj
2.0863 0 Td
(USA\),)Tj
2.6815 0 Td
(a)Tj
0.652 0 Td
(mix)Tj
1.7688 0 Td
(of)Tj
1.0148 0 Td
(sugars)Tj
2.7439 0 Td
(\(D-glucose,)Tj
4.8246 0 Td
(L-fucose,)Tj
3.8664 0 Td
(N-acetylglucosa-)Tj
-29.8089 -1.2983 Td
(mine,)Tj
2.5058 0 Td
(N-acetylgalactosamine;)Tj
9.4733 0 Td
(2.5)Tj
1.3946 0 Td
(mM)Tj
1.9332 0 Td
(each,)Tj
2.2507 0 Td
(Sigma-Aldrich\))Tj
6.4233 0 Td
(or)Tj
1.0998 0 Td
(glucose)Tj
3.1692 0 Td
(\(10)Tj
1.5136 0 Td
(mM,)Tj
2.16 0 Td
(Sigma-)Tj
-31.9235 -1.2983 Td
(Aldrich\).)Tj
3.8324 0 Td
(The)Tj
1.7801 0 Td
(medium)Tj
3.6057 0 Td
(without)Tj
3.3335 0 Td
(mucin)Tj
2.8063 0 Td
(was)Tj
1.6951 0 Td
(supplemented)Tj
5.8563 0 Td
(with)Tj
1.9956 0 Td
(tryptone)Tj
3.6397 0 Td
(\(8)Tj
1.0374 0 Td
(g/l,)Tj
1.4854 0 Td
(Oxoid)Tj
2.7326 0 Td
(Ltd,)Tj
-33.8001 -1.3039 Td
(Basingstoke,)Tj
5.1873 0 Td
(Hampshire,)Tj
4.9323 0 Td
(England\))Tj
3.9004 0 Td
(and)Tj
1.7291 0 Td
(L-threonine)Tj
5.023 0 Td
(\(2)Tj
1.0375 0 Td
(mM,)Tj
2.16 0 Td
(Sigma-Aldrich\).)Tj
6.6443 0 Td
(Incubations)Tj
4.9833 0 Td
(were)Tj
-35.5972 -1.2982 Td
(performed)Tj
4.4673 0 Td
(in)Tj
1.0375 0 Td
(serum)Tj
2.7212 0 Td
(bottles)Tj
2.863 0 Td
(sealed)Tj
2.6362 0 Td
(with)Tj
1.9956 0 Td
(butyl-rubber)Tj
5.3121 0 Td
(stoppers)Tj
3.5773 0 Td
(at)Tj
0.9524 0 Td
(37C)Tj
2.228 0 Td
(under)Tj
2.6192 0 Td
(anaerobic)Tj
4.1329 0 Td
(condi-)Tj
-34.5427 -1.2983 Td
(tions)Tj
2.1996 0 Td
(provided)Tj
3.8154 0 Td
(by)Tj
1.1849 0 Td
(a)Tj
0.652 0 Td
(gas)Tj
1.4796 0 Td
(phase)Tj
2.4832 0 Td
(of)Tj
1.0148 0 Td
(182)Tj
1.6497 0 Td
(kPa)Tj
1.7065 0 Td
(\(1.5)Tj
1.7404 0 Td
(atm\))Tj
2.109 0 Td
(N)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 407.7354 485.9149 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 411.307 487.6157 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(/CO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 428.7118 485.9149 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 434.4377 487.6157 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\(80/20)Tj
2.7949 0 Td
(ratio\).)Tj
2.6589 0 Td
(Growth)Tj
3.3278 0 Td
(was)Tj
1.6951 0 Td
(mea-)Tj
-33.919 -1.3039 Td
(sured)Tj
2.4321 0 Td
(by)Tj
1.1792 0 Td
(spectrophotometer)Tj
7.8179 0 Td
(as)Tj
1.0148 0 Td
(optical)Tj
2.914 0 Td
(density)Tj
3.1011 0 Td
(at)Tj
0.9467 0 Td
(600)Tj
1.6498 0 Td
(nm)Tj
1.5874 0 Td
(\(OD600\).)Tj
/F13 1 Tf
-21.4468 -1.2982 Td
[()31()6()7()7()11()12( )14()4()6()-4()11()2()-9( )12(\n)12()]TJ
6.9335 0 Td
[(\r)11()20()16(\n)-4()10()18( )14( )12( )]TJ
/F7 1 Tf
4.4447 0 Td
(A2-165)Tj
3.1578 0 Td
(was)Tj
1.6951 0 Td
(grown)Tj
2.7949 0 Td
(anaerobically)Tj
5.5218 0 Td
(at)Tj
0.9524 0 Td
(37C)Tj
2.2224 0 Td
(in)Tj
1.0374 0 Td
(YCFA)Tj
2.7269 0 Td
(medium)Tj
-32.6831 -1.2983 Td
(supplemented)Tj
5.8506 0 Td
(with)Tj
2.0013 0 Td
(33)Tj
1.1679 0 Td
(mM)Tj
1.9332 0 Td
(glucose)Tj
3.1748 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(].)Tj
/F13 1 Tf
2.0749 0 Td
[()-3()6()-4()11()13()4()6()1( )4()4()12(\n)-4()]TJ
5.3008 0 Td
[(\r)10()4()16()22()11()16()-9(\n)12()]TJ
/F7 1 Tf
4.3935 0 Td
(WCFS1)Tj
3.3279 0 Td
(was)Tj
1.7008 0 Td
(grown)Tj
2.7949 0 Td
(aerobi-)Tj
-33.7206 -1.2983 Td
(cally)Tj
2.0239 0 Td
(and)Tj
/F13 1 Tf
1.7291 0 Td
[()17( )12()-8( )4()4()13()4()6()-4()11()2()-9( )12(\n)12()]TJ
6.5083 0 Td
[()11()20()-5()3()]TJ
/F7 1 Tf
2.2791 0 Td
(DSM-20213)Tj
5.0513 0 Td
(anaerobically)Tj
5.5162 0 Td
(at)Tj
0.9523 0 Td
(37C)Tj
2.228 0 Td
(in)Tj
1.0375 0 Td
(Difco)Tj
/F14 1 Tf
[()]TJ
/F7 1 Tf
2.8913 0 Td
(Lactobacilli)Tj
4.8132 0 Td
(MRS)Tj
-35.0302 -1.3039 Td
(broth)Tj
2.4321 0 Td
(\(Becton)Tj
3.3392 0 Td
(Dickinson,)Tj
4.5977 0 Td
(Sparks,)Tj
3.1011 0 Td
(USA\).)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 393.7889 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Peripheral)Tj
4.7149 0 Td
(blood)Tj
2.6268 0 Td
(mononuclear)Tj
5.9292 0 Td
(cells)Tj
2.1922 0 Td
(assay)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 376.7811 cm
BT
/F7 1 Tf
1 TL
-0.015 Tc
0 0 Td
(Peripheral)Tj
4.2519 0 Td
(blood)Tj
2.4548 0 Td
(of)Tj
0.9978 0 Td
(three)Tj
2.2053 0 Td
(healthy)Tj
3.0557 0 Td
(donors)Tj
2.9764 0 Td
(was)Tj
1.6668 0 Td
(received)Tj
3.4469 0 Td
(from)Tj
2.16 0 Td
(the)Tj
1.4399 0 Td
(Sanquin)Tj
3.4526 0 Td
(Blood)Tj
2.5285 0 Td
(Bank,)Tj
2.4491 0 Td
(Nijmegen,)Tj
-33.0857 -1.2982 Td
(The)Tj
1.7461 0 Td
(Netherlands.)Tj
5.2157 0 Td
(Peripheral)Tj
4.2463 0 Td
(blood)Tj
2.4604 0 Td
(mononuclear)Tj
5.4595 0 Td
(cells)Tj
1.8652 0 Td
(\(PBMCs\))Tj
3.8778 0 Td
(were)Tj
2.0806 0 Td
(separated)Tj
3.9118 0 Td
(from)Tj
2.16 0 Td
(the)Tj
1.4343 0 Td
(blood)Tj
-34.4577 -1.2983 Td
(of)Tj
0.9921 0 Td
(healthy)Tj
3.0557 0 Td
(donors)Tj
2.9764 0 Td
(using)Tj
2.3357 0 Td
(Ficoll-Paque)Tj
5.108 0 Td
(Plus)Tj
1.8652 0 Td
(gradient)Tj
3.4696 0 Td
(centrifugation)Tj
5.7316 0 Td
(according)Tj
4.0932 0 Td
(to)Tj
1.0034 0 Td
(the)Tj
1.4344 0 Td
(manufac-)Tj
-32.0653 -1.3039 Td
(turer's)Tj
2.7099 0 Td
(protocol)Tj
3.5092 0 Td
(\(Amersham)Tj
4.9039 0 Td
(biosciences,)Tj
4.8246 0 Td
(Uppsala,)Tj
3.6056 0 Td
(Sweden\).)Tj
3.7757 0 Td
(After)Tj
2.2337 0 Td
(centrifugation)Tj
5.7316 0 Td
(the)Tj
1.44 0 Td
(mononu-)Tj
-32.7342 -1.2983 Td
(clear)Tj
2.0636 0 Td
(cells)Tj
1.8651 0 Td
(were)Tj
2.075 0 Td
(collected,)Tj
3.8551 0 Td
(washed)Tj
3.1124 0 Td
(in)Tj
1.0148 0 Td
(Iscove's)Tj
3.2201 0 Td
(Modified)Tj
3.8325 0 Td
(Dulbecco's)Tj
4.4787 0 Td
(Medium)Tj
3.6113 0 Td
(\(IMDM\))Tj
3.6963 0 Td
(+)Tj
0.7881 0 Td
(Glutamax)Tj
-33.613 -1.2982 Td
(\(Invitrogen,)Tj
4.8755 0 Td
(Breda,)Tj
2.7156 0 Td
(The)Tj
1.7518 0 Td
(Netherlands\))Tj
5.3234 0 Td
(and)Tj
1.7008 0 Td
(adjusted)Tj
3.4866 0 Td
(to)Tj
1.0034 0 Td
(0.5)Tj
/F14 1 Tf
1.3663 0 Td
[()]TJ
/F7 1 Tf
0.7767 0 Td
(10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 439.3133 316.233 cm
BT
/F7 1 Tf
1 TL
-0.02 Tc
0 0 Td
(6)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 444.9259 311.811 cm
BT
/F7 1 Tf
1 TL
-0.015 Tc
0 0 Td
(cells/ml)Tj
3.2314 0 Td
(in)Tj
1.0148 0 Td
(IMDM)Tj
3.0331 0 Td
(+)Tj
0.7937 0 Td
(Glutamax)Tj
-32.5641 -1.2982 Td
(supplemented)Tj
5.7202 0 Td
(with)Tj
1.9559 0 Td
(penicillin)Tj
3.8665 0 Td
(\(100)Tj
1.9389 0 Td
(U/ml\))Tj
2.6362 0 Td
(\(Invitrogen\),)Tj
5.21 0 Td
(streptomycin)Tj
5.38 0 Td
(\(100)Tj
/F14 1 Tf
1.9389 0 Td
[()]TJ
/F7 1 Tf
(g/ml\))Tj
2.863 0 Td
(\(Invitrogen\),)Tj
-31.5096 -1.3039 Td
(and)Tj
1.6951 0 Td
(10%)Tj
1.8935 0 Td
(heat)Tj
1.8595 0 Td
(inactivated)Tj
4.4787 0 Td
(Fetal)Tj
2.092 0 Td
(Bovine)Tj
2.9367 0 Td
(Serum)Tj
2.7836 0 Td
(\(FBS,)Tj
2.313 0 Td
(Lonza,)Tj
2.8233 0 Td
(Basel,)Tj
2.4207 0 Td
(Switzerland\).)Tj
5.3348 0 Td
(PBMCs)Tj
-30.6309 -1.2983 Td
(\(0.5)Tj
/F14 1 Tf
1.6894 0 Td
[()]TJ
/F7 1 Tf
0.7824 0 Td
(10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 234.0283 277.2283 cm
BT
/F7 1 Tf
1 TL
-0.02 Tc
0 0 Td
(6)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 239.6409 272.8062 cm
BT
/F7 1 Tf
1 TL
-0.015 Tc
0 0 Td
(cells/well\))Tj
4.0705 0 Td
(were)Tj
2.0806 0 Td
(seeded)Tj
2.8403 0 Td
(in)Tj
1.0091 0 Td
(48-well)Tj
3.0501 0 Td
(tissue)Tj
2.3924 0 Td
(culture)Tj
2.9594 0 Td
(plates.)Tj
-0.004 Tc
-21.1689 -1.2982 Td
(Per)Tj
-0.018 Tc
1.576 0 Td
(donor)Tj
2.6134 0 Td
(a)Tj
0.6407 0 Td
(negative)Tj
3.4185 0 Td
(control)Tj
3.0274 0 Td
(\(just)Tj
1.9332 0 Td
(medium\),)Tj
4.0592 0 Td
(and)Tj
1.6894 0 Td
(a)Tj
0.635 0 Td
(positive)Tj
3.2088 0 Td
(control)Tj
3.0217 0 Td
(\(LPS)Tj
2.075 0 Td
(from)Tj
/F13 1 Tf
2.1486 0 Td
[()]TJ
/F7 1 Tf
(.)Tj
/F13 1 Tf
0.9695 0 Td
[()7()10()12( )]TJ
/F7 1 Tf
1.5023 0 Td
(1)Tj
/F14 1 Tf
0.6803 0 Td
[()]TJ
/F7 1 Tf
(g/ml\))Tj
-34.3953 -1.3039 Td
(were)Tj
2.0636 0 Td
(used.)Tj
2.2166 0 Td
(PBMCs)Tj
3.2088 0 Td
(were)Tj
2.0636 0 Td
(stimulated)Tj
4.286 0 Td
(with)Tj
1.9389 0 Td
(live)Tj
1.5534 0 Td
(bacteria)Tj
3.2711 0 Td
(or)Tj
1.0658 0 Td
(bacterial)Tj
3.5036 0 Td
(fractions.)Tj
3.7984 0 Td
(For)Tj
1.5874 0 Td
(the)Tj
1.4287 0 Td
(heat-killed)Tj
-31.9859 -1.2983 Td
(cells)Tj
1.8482 0 Td
(the)Tj
1.4287 0 Td
(bacterial)Tj
3.4978 0 Td
(culture)Tj
2.9423 0 Td
(was)Tj
1.6555 0 Td
(kept)Tj
1.8992 0 Td
(at)Tj
0.9241 0 Td
(99C)Tj
2.1713 0 Td
(for)Tj
1.3436 0 Td
(10)Tj
1.1452 0 Td
(min.)Tj
2.0239 0 Td
(The)Tj
1.7405 0 Td
(ratio)Tj
2.0296 0 Td
(of)Tj
0.9864 0 Td
(PBMC)Tj
2.8573 0 Td
(to)Tj
0.9978 0 Td
(bacteria)Tj
3.2655 0 Td
(was)Tj
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(1:10.)Tj
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