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Isaque Medeiros Siqueira, Raffael Júnio Araújo de Castro, Luiza Chaves de Miranda Leonhardt, Márcio Sousa Jerônimo, Aluízio Carlos Soares, Tainá Raiol, Christiane Nishibe, Nalvo Almeida, Aldo Henrique Tavares, Christian Hoffmann, Anamelia Lorenzetti Bocca
Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity
www.plosntds.org
www.plosntds.org
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3.4753 0 Td
(by)Tj
1.1792 0 Td
(cells)Tj
1.9218 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(innate)Tj
2.7439 0 Td
(immune)Tj
-34.1062 -1.2983 Td
(system)Tj
2.9366 0 Td
(occurs)Tj
2.8347 0 Td
(mainly)Tj
2.9876 0 Td
(through)Tj
3.447 0 Td
(the)Tj
1.4683 0 Td
(engagement)Tj
5.074 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(C-type)Tj
2.9253 0 Td
(lectin)Tj
2.4265 0 Td
(receptors)Tj
3.9174 0 Td
(\(CLRs\))Tj
3.0841 0 Td
(Dectin-1)Tj
-33.5846 -1.2983 Td
(and)Tj
1.7234 0 Td
(Dectin-2)Tj
3.7417 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(].)Tj
/F13 1 Tf
2.0693 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F13 1 Tf
0.9581 0 Td
[()4()7( )12(\n)20()7()-3()11()]TJ
/F8 1 Tf
3.4696 0 Td
(conidia)Tj
3.1918 0 Td
(\(FC\))Tj
2.0863 0 Td
(are)Tj
1.4456 0 Td
(unable)Tj
2.9027 0 Td
(to)Tj
1.0204 0 Td
(promote)Tj
3.6567 0 Td
(the)Tj
1.4683 0 Td
(release)Tj
2.897 0 Td
(of)Tj
1.0092 0 Td
(pro-inflamma-)Tj
-31.6401 -1.3039 Td
(tory)Tj
1.8481 0 Td
(cytokines,)Tj
4.2293 0 Td
(such)Tj
2.0579 0 Td
(as)Tj
1.0148 0 Td
(TNF-)Tj
/F14 1 Tf
()Tj
/F8 1 Tf
(,)Tj
3.2428 0 Td
(which)Tj
2.6476 0 Td
(is)Tj
0.8504 0 Td
(only)Tj
1.9729 0 Td
(re-instated)Tj
4.524 0 Td
(after)Tj
2.0353 0 Td
(Toll)Tj
1.8312 0 Td
(like)Tj
1.6554 0 Td
(receptor)Tj
3.5546 0 Td
(\(TLR\))Tj
2.6702 0 Td
(co-stim-)Tj
-34.1345 -1.2982 Td
(ulation)Tj
3.05 0 Td
([)Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
(].)Tj
2.075 0 Td
(Studies)Tj
3.101 0 Td
(of)Tj
/F13 1 Tf
1.0148 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F13 1 Tf
0.9638 0 Td
[()4()7( )12(\n)20()7()-3()11()]TJ
/F8 1 Tf
(,)Tj
3.6964 0 Td
(mostly)Tj
2.9083 0 Td
(making)Tj
3.2485 0 Td
(use)Tj
1.5307 0 Td
(of)Tj
1.0148 0 Td
(its)Tj
1.1508 0 Td
(conidial)Tj
3.4413 0 Td
(form,)Tj
2.4264 0 Td
(have)Tj
2.0636 0 Td
(thus)Tj
1.9332 0 Td
(far)Tj
1.3153 0 Td
(been)Tj
-34.9339 -1.2983 Td
(unable)Tj
2.9083 0 Td
(to)Tj
1.0204 0 Td
(completely)Tj
4.5808 0 Td
(elucidate)Tj
3.7927 0 Td
(the)Tj
1.4684 0 Td
(pathogenesis)Tj
5.3574 0 Td
(of)Tj
1.0148 0 Td
(CBM,)Tj
2.5795 0 Td
(leaving)Tj
3.0614 0 Td
(a)Tj
0.652 0 Td
(gap)Tj
1.6384 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.4683 0 Td
(understanding)Tj
6.0718 0 Td
(of)Tj
-36.646 -1.3039 Td
(the)Tj
1.4683 0 Td
(disease)Tj
3.016 0 Td
(progression)Tj
4.9209 0 Td
(and)Tj
1.7292 0 Td
(the)Tj
1.474 0 Td
(markedly)Tj
3.9911 0 Td
(chronic)Tj
3.2882 0 Td
(inflammatory)Tj
5.7089 0 Td
(response)Tj
3.7304 0 Td
(observed)Tj
3.7984 0 Td
(in)Tj
1.0375 0 Td
(CBM)Tj
-34.1629 -1.2983 Td
([)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(20)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(22)Tj
0 g
(].)Tj
1.1962 -1.2982 Td
(In)Tj
1.1111 0 Td
(this)Tj
1.6725 0 Td
(study)Tj
2.3924 0 Td
(we)Tj
1.3266 0 Td
(show)Tj
2.3017 0 Td
(that)Tj
/F13 1 Tf
1.7745 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F13 1 Tf
0.9638 0 Td
[()4()7( )12(\n)20()7()-3()11()]TJ
/F8 1 Tf
3.4752 0 Td
(hyphae)Tj
3.1011 0 Td
(\(FH\))Tj
2.1997 0 Td
(and)Tj
1.7291 0 Td
(muriform)Tj
4.1896 0 Td
(cells)Tj
1.9219 0 Td
(are)Tj
1.4456 0 Td
(able)Tj
1.8312 0 Td
(to)Tj
1.0261 0 Td
(establish)Tj
-33.6583 -1.2983 Td
(a)Tj
0.6519 0 Td
(murine)Tj
3.1805 0 Td
(CBM)Tj
2.3527 0 Td
(displaying)Tj
4.3086 0 Td
(skin)Tj
1.8936 0 Td
(lesions)Tj
2.9366 0 Td
(and)Tj
1.7292 0 Td
(histopathological)Tj
7.0525 0 Td
(features)Tj
3.3506 0 Td
(similar)Tj
2.982 0 Td
(to)Tj
1.0261 0 Td
(that)Tj
1.7802 0 Td
(found)Tj
2.6192 0 Td
(in)Tj
-35.8637 -1.3039 Td
(humans,)Tj
3.6623 0 Td
(with)Tj
1.9956 0 Td
(muriform)Tj
4.1952 0 Td
(cells)Tj
1.9219 0 Td
(being)Tj
2.4264 0 Td
(the)Tj
1.474 0 Td
(most)Tj
2.2054 0 Td
(persistent)Tj
4.0875 0 Td
(fungal)Tj
2.7326 0 Td
(morphotype,)Tj
5.3858 0 Td
(whereas)Tj
3.4469 0 Td
(mice)Tj
-33.5336 -1.2983 Td
(infected)Tj
3.4185 0 Td
(with)Tj
/F13 1 Tf
1.9956 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F13 1 Tf
0.9638 0 Td
[()4()7( )12(\n)20()7()-3()11()]TJ
/F8 1 Tf
3.4752 0 Td
(conidia)Tj
3.1918 0 Td
(do)Tj
1.2586 0 Td
(not)Tj
1.5704 0 Td
(reach)Tj
2.3981 0 Td
(the)Tj
1.474 0 Td
(chronic)Tj
3.2881 0 Td
(phase)Tj
2.4832 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(disease.)Tj
3.2428 0 Td
(Furthermore,)Tj
-31.2432 -1.2983 Td
(the)Tj
1.4683 0 Td
(presence)Tj
3.7133 0 Td
(of)Tj
1.0148 0 Td
(hyphae)Tj
3.1011 0 Td
(and)Tj
1.7348 0 Td
(especially)Tj
4.0139 0 Td
(muriform)Tj
4.1952 0 Td
(cells,)Tj
2.143 0 Td
(but)Tj
1.5534 0 Td
(not)Tj
1.576 0 Td
(conidia,)Tj
3.4186 0 Td
(is)Tj
0.8504 0 Td
(correlated)Tj
4.2462 0 Td
(with)Tj
-33.029 -1.3039 Td
(intense)Tj
3.0897 0 Td
(production)Tj
4.7168 0 Td
(of)Tj
1.0148 0 Td
(pro-inflammatory)Tj
7.4551 0 Td
(cytokines)Tj
/F13 1 Tf
3.9968 0 Td
[()12()]TJ
1.0148 0 Td
[()-13()15()3()]TJ
/F8 1 Tf
(.)Tj
2.0466 0 Td
(High-throughput)Tj
7.1659 0 Td
(RNA)Tj
2.2621 0 Td
(sequencing)Tj
-32.7626 -1.2982 Td
(analysis)Tj
3.3278 0 Td
(showed)Tj
3.2485 0 Td
(distinct)Tj
3.2088 0 Td
(patterns)Tj
3.4752 0 Td
(of)Tj
1.0148 0 Td
(gene)Tj
2.0807 0 Td
(expression)Tj
4.4673 0 Td
(dependent)Tj
4.4561 0 Td
(on)Tj
1.2755 0 Td
(the)Tj
1.4684 0 Td
(fungal)Tj
2.7326 0 Td
(form)Tj
2.2053 0 Td
(interaction)Tj
-32.961 -1.2983 Td
(used:)Tj
2.2847 0 Td
(macrophages)Tj
5.5048 0 Td
(exposed)Tj
3.4412 0 Td
(to)Tj
1.0262 0 Td
(muriform)Tj
4.1952 0 Td
(cells,)Tj
2.143 0 Td
(but)Tj
1.5534 0 Td
(not)Tj
1.576 0 Td
(conidia,)Tj
3.4186 0 Td
(exhibited)Tj
3.9288 0 Td
(a)Tj
0.652 0 Td
(strong)Tj
2.7722 0 Td
(up-regula-)Tj
-32.4961 -1.3039 Td
(tion)Tj
1.8425 0 Td
(of)Tj
1.0148 0 Td
(genes)Tj
2.4377 0 Td
(related)Tj
2.948 0 Td
(to)Tj
1.0205 0 Td
(fungal)Tj
2.7326 0 Td
(recognition,)Tj
5.074 0 Td
(cell)Tj
1.559 0 Td
(migration,)Tj
4.422 0 Td
(inflammation)Tj
5.6976 0 Td
(and)Tj
1.7292 0 Td
(apoptosis.)Tj
4.2179 0 Td
(Alto-)Tj
-34.6958 -1.2983 Td
(gether,)Tj
2.9536 0 Td
(our)Tj
1.6271 0 Td
(findings)Tj
3.4923 0 Td
(reveal)Tj
2.5738 0 Td
(two)Tj
1.7065 0 Td
(different)Tj
3.6566 0 Td
(fungal-host)Tj
4.7735 0 Td
(interaction)Tj
4.6091 0 Td
(strategies)Tj
3.9232 0 Td
(according)Tj
4.1896 0 Td
(to)Tj
1.0261 0 Td
(fungal)Tj
-34.5314 -1.2983 Td
(form,)Tj
2.4321 0 Td
(highlighting)Tj
5.091 0 Td
(fungal)Tj
2.7325 0 Td
(dimorphism)Tj
5.2044 0 Td
(as)Tj
1.0148 0 Td
(an)Tj
1.2019 0 Td
(important)Tj
4.2803 0 Td
(key)Tj
1.593 0 Td
(in)Tj
1.0375 0 Td
(understanding)Tj
6.0718 0 Td
(the)Tj
1.4683 0 Td
(bipolar)Tj
-32.1276 -1.2982 Td
(nature)Tj
2.8232 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(inflammatory)Tj
5.7089 0 Td
(response)Tj
3.7304 0 Td
(in)Tj
1.0375 0 Td
(fungal)Tj
2.7325 0 Td
(infections.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 325.9842 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
(Fungal)Tj
3.2362 0 Td
(strain)Tj
2.6362 0 Td
(and)Tj
1.8662 0 Td
(infection)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 291.0047 cm
BT
/F13 1 Tf
1 TL
-0.004 Tc
0 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F13 1 Tf
0.9637 0 Td
[()4()7( )12(\n)20()7()-3()11()]TJ
/F8 1 Tf
3.4696 0 Td
(\(ATCC)Tj
3.1805 0 Td
(46428\))Tj
2.9423 0 Td
(was)Tj
1.6951 0 Td
(cultivated)Tj
4.1216 0 Td
(in)Tj
1.0374 0 Td
(Sabouraud)Tj
4.5298 0 Td
(Dextrose)Tj
3.8097 0 Td
(Agar)Tj
2.1713 0 Td
(medium)Tj
3.6057 0 Td
(\(SDA,)Tj
2.6815 0 Td
(Hime-)Tj
-34.2082 -1.2982 Td
(dia\))Tj
1.7858 0 Td
(supplemented)Tj
5.8563 0 Td
(with)Tj
1.9956 0 Td
(100)Tj
1.6497 0 Td
(mg.l)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 330.4629 282.444 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(-1)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 338.7968 278.022 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(chloramphenicol)Tj
7.0128 0 Td
(at)Tj
0.9525 0 Td
(37C,)Tj
2.4491 0 Td
(as)Tj
1.0148 0 Td
(described)Tj
4.0535 0 Td
(previously)Tj
4.354 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(].)Tj
-33.715 -1.3039 Td
(Fungal)Tj
2.9707 0 Td
(virulence)Tj
3.9061 0 Td
(and)Tj
1.7291 0 Td
(strain)Tj
2.5002 0 Td
(adaptation)Tj
4.4843 0 Td
(to)Tj
1.0261 0 Td
(an)Tj
1.2019 0 Td
(animal)Tj
2.9707 0 Td
(host)Tj
1.9105 0 Td
(was)Tj
1.7008 0 Td
(acquired)Tj
3.702 0 Td
(by)Tj
1.1849 0 Td
(sequentially)Tj
4.9549 0 Td
(inocu-)Tj
-34.2422 -1.2982 Td
(lating)Tj
/F13 1 Tf
2.4775 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F13 1 Tf
0.9638 0 Td
[()4()7( )12(\n)20()7()-3()11()]TJ
/F8 1 Tf
3.4695 0 Td
(propagules)Tj
4.5921 0 Td
(three)Tj
2.2677 0 Td
(times)Tj
2.3867 0 Td
(into)Tj
1.8425 0 Td
(experimental)Tj
5.4595 0 Td
(animal)Tj
2.965 0 Td
(footpads)Tj
3.6624 0 Td
(at)Tj
0.9524 0 Td
(2x10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 529.3417 256.422 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(7)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 535.0677 252 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(cells)Tj
1.9218 0 Td
(per)Tj
-35.4271 -1.2982 Td
(ml)Tj
1.287 0 Td
(\(50)Tj
/F15 1 Tf
1.508 0 Td
[()]TJ
/F8 1 Tf
(l)Tj
0.9751 0 Td
(per)Tj
1.5307 0 Td
(foot\),)Tj
2.3868 0 Td
(followed)Tj
3.651 0 Td
(by)Tj
1.1792 0 Td
(strain)Tj
2.5001 0 Td
(recovery)Tj
3.651 0 Td
(15)Tj
1.1679 0 Td
(days)Tj
2.0012 0 Td
(later)Tj
1.9899 0 Td
(in)Tj
1.0375 0 Td
(SDA)Tj
2.1146 0 Td
(medium.)Tj
-25.7837 -1.3039 Td
(Purified)Tj
3.4525 0 Td
(conidia)Tj
3.1975 0 Td
(and)Tj
1.7291 0 Td
(hyphae)Tj
3.1068 0 Td
(were)Tj
2.1203 0 Td
(obtained)Tj
3.736 0 Td
(by)Tj
1.1792 0 Td
(growing)Tj
3.5263 0 Td
(virulent)Tj
/F13 1 Tf
3.3619 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F13 1 Tf
0.9581 0 Td
[()4()7( )12(\n)20()7()-3()11()]TJ
/F8 1 Tf
3.4752 0 Td
(propagules)Tj
4.592 0 Td
(in)Tj
-35.6312 -1.2983 Td
(potato)Tj
2.778 0 Td
(dextrose)Tj
3.6 0 Td
(medium)Tj
3.6056 0 Td
(in)Tj
1.0375 0 Td
(a)Tj
0.6519 0 Td
(rotary)Tj
2.6589 0 Td
(shaker)Tj
2.829 0 Td
(\(120)Tj
1.9899 0 Td
(rpm\))Tj
2.2677 0 Td
(at)Tj
0.9524 0 Td
(37C)Tj
2.228 0 Td
(for)Tj
1.3833 0 Td
(714)Tj
2.1657 0 Td
(days.)Tj
2.2224 0 Td
(At)Tj
1.2018 0 Td
(that)Tj
1.7802 0 Td
(time,)Tj
2.2562 0 Td
(cul-)Tj
-35.6085 -1.2983 Td
(ture)Tj
1.8426 0 Td
(suspensions)Tj
5.0002 0 Td
(containing)Tj
4.5298 0 Td
(conidia)Tj
3.1918 0 Td
(and)Tj
1.7291 0 Td
(hyphal)Tj
2.931 0 Td
(fragments)Tj
4.2293 0 Td
(were)Tj
2.1203 0 Td
(first)Tj
1.8085 0 Td
(filtered)Tj
3.067 0 Td
(in)Tj
1.0318 0 Td
(sterile)Tj
2.6135 0 Td
(fiber-)Tj
-34.0949 -1.3039 Td
(glass)Tj
2.0863 0 Td
(to)Tj
1.0262 0 Td
(remove)Tj
3.2201 0 Td
(large)Tj
2.16 0 Td
(hyphae)Tj
3.1011 0 Td
(clumps.)Tj
3.3448 0 Td
(The)Tj
1.7802 0 Td
(filtrate)Tj
2.846 0 Td
(was)Tj
1.7007 0 Td
(subjected)Tj
3.9685 0 Td
(to)Tj
1.0261 0 Td
(successive)Tj
4.2463 0 Td
(filtrations)Tj
4.1045 0 Td
(on)Tj
-34.6108 -1.2982 Td
(70)Tj
/F15 1 Tf
1.1679 0 Td
[()]TJ
/F8 1 Tf
(m)Tj
1.5477 0 Td
(and)Tj
1.7291 0 Td
(40)Tj
/F15 1 Tf
1.1736 0 Td
[()]TJ
/F8 1 Tf
(m)Tj
1.5477 0 Td
(cell)Tj
1.559 0 Td
(strainers)Tj
3.6567 0 Td
(\(BD\).)Tj
2.4378 0 Td
(Retained)Tj
3.7644 0 Td
(hyphae)Tj
3.1067 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(40)Tj
/F15 1 Tf
1.1736 0 Td
[()]TJ
/F8 1 Tf
(m)Tj
1.542 0 Td
(cell)Tj
1.5591 0 Td
(strainer)Tj
3.2995 0 Td
(\(measuring)Tj
4.779 0 Td
(40)Tj
-0.02 Tc
-36.5496 -1.2983 Td
(to)Tj
0.9922 0 Td
(70)Tj
/F15 1 Tf
1.1395 0 Td
[()]TJ
/F8 1 Tf
(m\))Tj
1.8368 0 Td
(were)Tj
2.058 0 Td
(re-suspended)Tj
5.3914 0 Td
(in)Tj
1.0035 0 Td
(phosphate)Tj
4.1896 0 Td
(buffered)Tj
3.4525 0 Td
(saline)Tj
2.4038 0 Td
(\(PBS\))Tj
2.4321 0 Td
(and)Tj
1.6838 0 Td
(centrifuged)Tj
4.6091 0 Td
(twice)Tj
2.2393 0 Td
(at)Tj
0.9184 0 Td
(1000)Tj
2.0579 0 Td
(g,)Tj
-36.4079 -1.2983 Td
(providing)Tj
4.0025 0 Td
(more)Tj
2.2734 0 Td
(than)Tj
1.9672 0 Td
(98%)Tj
1.8822 0 Td
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