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Cellular Microbiology: Pathogen-Host Cell Molecular Interactions

Trypanosoma cruzi Produces the Specialized Proresolving Mediators Resolvin D1, Resolvin D5, and Resolvin E2

Romain A. Colas, Anthony W. Ashton, Shankar Mukherjee, Jesmond Dalli, Oscar B. Akide-Ndunge, Huan Huang, Mahalia S. Desruisseaux, Fangxia Guan, Linda A. Jelicks, Fabiane Matos dos Santos, Jyothi Nagajyothi, Michael A. Zingman, Jinet Reyes, Louis M. Weiss, Charles N. Serhan, Herbert B. Tanowitz
Judith A. Appleton, Editor
Romain A. Colas
aCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
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Anthony W. Ashton
bKolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, NSW, Australia
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Shankar Mukherjee
cDepartment of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA
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Jesmond Dalli
aCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
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Oscar B. Akide-Ndunge
cDepartment of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA
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  • ORCID record for Oscar B. Akide-Ndunge
Huan Huang
cDepartment of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA
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Mahalia S. Desruisseaux
cDepartment of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA
dDepartment of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA
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Fangxia Guan
cDepartment of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA
gSchool of Life Sciences, Zhengzhou University, Zhengzhou, China
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Linda A. Jelicks
eDepartment of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York, USA
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Fabiane Matos dos Santos
cDepartment of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA
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Jyothi Nagajyothi
fPublic Health Research Institute Center at the International Center for Public Health, New Jersey Medical School—Rutgers, The State University of New Jersey, Rutgers, New Jersey, USA
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Michael A. Zingman
cDepartment of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA
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Jinet Reyes
cDepartment of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA
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Louis M. Weiss
cDepartment of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA
dDepartment of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA
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Charles N. Serhan
aCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
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Herbert B. Tanowitz
cDepartment of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA
dDepartment of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA
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Judith A. Appleton
Cornell University
Roles: Editor
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DOI: 10.1128/IAI.00688-17
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  • FIG 1
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    FIG 1

    Kinetics of cardiomyopathy in T. cruzi infection. (A and B) Parasitemia (A) and mortality (B) in CD-1 mice infected with 5 × 104 trypomastigotes of T. cruzi strain Brazil. (C and D) Representative cardiac MRIs of control (C) and infected (D) mouse hearts revealing an enlarged right ventricle (RV). (E and F) Representative histopathology of the heart during acute and chronic infection showing pseudocysts of amastigotes (arrows) and inflammation. The images are representative of groups of 5 mice each. **, P ≤ 0.05.

  • FIG 2
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    FIG 2

    T. cruzi is a source of RvD1 during infection. (A) Serum RvD1 levels in mice inoculated with 5 × 104 strain Brazil trypomastigotes. The data are means and standard deviations (SD) (n = 5). The asterisks indicate significant differences (**, P ≤ 0.05) from uninfected mice. (B) Release of RvD1 from T. cruzi, related protists, and infected L6E9 cells. RvD1 release was measured by ELISA from conditioned medium. The data are means and SD (n = 3). The asterisks indicate significant differences (**, P ≤ 0.05) from epimastigotes and uninfected L6E9 cells. Epis, epimastigote forms of strain Tulahuen; Trypos, trypomastigotes of strains Brazil and Tulahuen; Toxo, lysates of T. gondii strain RH; Uninf and Inf, L6E9 myoblasts uninfected or infected with trypomastigotes of T. cruzi strain Tulahuen, respectively.

  • FIG 3
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    FIG 3

    Representative spectra used to identify lipid mediators of the resolving class and LC–MS-MS fragmentation spectra employed for the identification of RvD1, RvD5, and RvE2 in lysates of trypomastigotes of T. cruzi from strains Brazil and Tulahuen.

Tables

  • Figures
  • TABLE 1

    Quantitation of FFA precursors in lysates of trypomastigotes by LC–MS-MS

    FFA precursor speciesaMass (m/z) of diagnostic ions at quadrupole position (Q):Amt in trypomastigotes of T. cruzi strainb:
    Q1Q3TulahuenBrazil
    EPA3012571.6–1,194c2.9–1,937c
    DHA327283113–15,111c62.1–3,841c
    4S,14S-diHDHA359221−−
    17-HDHA3432459.7–199.36.4–242.4
    14-HDHA34320515.7–86.814.9–141.6
    7-HDHA34314116.9–262.411.3–88.2
    4-HDHA34310194.5–427.470.0–471.3
    AA30325915.5–2,529c32–5,766c
    • ↵a HDHA, hydroxydocosahexaenoic acid; AA, arachidonic acid.

    • ↵b Expression of lipid species quantified from peak height and expressed as picograms per milligram of protein. The data represent the range of samples documented from 3 independent lysates for each strain. −, sample with value below the detection limit.

    • ↵c Amount in nanograms per milligram of protein.

  • TABLE 2

    Quantitation of prostaglandin species in lysates of trypomastigotes of T. cruzi by LC–MS-MS

    Prostaglandin lipid speciesaMass (m/z) of diagnostic ions at quadrupole position (Q):Amt in trypomastigotes of T. cruzi strainb:
    Q1Q3TulahuenBrazil
    PGD23511891.4–3.92.7–23
    PGE23511892.0–21.46.0–48.6
    PGF2α3531932.6–38.92.7–2.6
    • ↵a PG, prostaglandin.

    • ↵b Expression of lipid species quantified from peak height and expressed as picograms per milligram of protein. The data represent the range of samples documented from 3 independent lysates for each strain.

  • TABLE 3

    Quantitation of lipoxygenase-derived lipid species in lysates of T. cruzi trypomastigotes by LC–MS-MS

    Lipoxygenase-derived lipid speciesaMass (m/z) of diagnostic ions at quadrupole position (Q):Amt in trypomastigotes of T. cruzi strainb:
    Q1Q3TulahuenBrazil
    LTB4335195−−
    20-OH-LTB4351195−−
    20-COOH-LTB4365195−−
    5-HETE31911554.6–101.626.3–122.1
    12-HETE31917911.1–46.915.3–143.3
    15-HETE31921924.8–166.439.7–328.1
    5S,15S-diHETE3352352.3–5.25.7–8.0
    5-HEPE3171155.4–12.92.5–31.0
    12-HEPE3171790.7–6.10.6–1.0
    15-HEPE3172192.5–3.32.3–3.4
    18-HEPE3172593.8–5.41.7–2.2
    5S,15S-diHEPE3331151.3–27.71.7–13.6
    • ↵a LT, leukotriene.

    • ↵b Expression of lipid species quantified from peak height and expressed as picograms per milligram of protein. The data represent the range of samples documented from 3 independent lysates for each strain. −, sample with value below the detection limit.

  • TABLE 4

    Quantitation of proresolving lipid mediators in lysates of trypomastigotes of T. cruzi by LC–MS-MS

    Proresolving lipid speciesaMass (m/z) of diagnostic ions at quadrupole position (Q):Amt in trypomastigotes of T .cruzi strainb:
    Q1Q3TulahuenBrazil
    RvD13751411.2–1.41.8–7.0
    RvD2375215−−
    RvD3375147−−
    RvD53591991.4–1.60.7–1.9
    RvD6359159−−
    RvE1349161−−
    RvE2333253−9.5–23.6
    RvE3333201−−
    PD1359153−−
    22-OH-PD1375153−−
    22-COOH-PD1389153−−
    MaR1359250−−
    LXA4351115−−
    LXB4351115−−
    LXA5349215−−
    LXB5349221−−
    • ↵a RvD, resolvins derived from docosahexenoic acid; RvE, resolvins derived from eicosapentaenoic acid; PD, protectin; MaR, maresin; LX, lipoxin.

    • ↵b Expression of lipid species quantified from peak height and expressed as picograms per milligram of protein. The data represent the range of samples documented from 3 independent lysates for each strain. −, sample with value below the detection limit.

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Trypanosoma cruzi Produces the Specialized Proresolving Mediators Resolvin D1, Resolvin D5, and Resolvin E2
Romain A. Colas, Anthony W. Ashton, Shankar Mukherjee, Jesmond Dalli, Oscar B. Akide-Ndunge, Huan Huang, Mahalia S. Desruisseaux, Fangxia Guan, Linda A. Jelicks, Fabiane Matos dos Santos, Jyothi Nagajyothi, Michael A. Zingman, Jinet Reyes, Louis M. Weiss, Charles N. Serhan, Herbert B. Tanowitz
Infection and Immunity Mar 2018, 86 (4) e00688-17; DOI: 10.1128/IAI.00688-17

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Trypanosoma cruzi Produces the Specialized Proresolving Mediators Resolvin D1, Resolvin D5, and Resolvin E2
Romain A. Colas, Anthony W. Ashton, Shankar Mukherjee, Jesmond Dalli, Oscar B. Akide-Ndunge, Huan Huang, Mahalia S. Desruisseaux, Fangxia Guan, Linda A. Jelicks, Fabiane Matos dos Santos, Jyothi Nagajyothi, Michael A. Zingman, Jinet Reyes, Louis M. Weiss, Charles N. Serhan, Herbert B. Tanowitz
Infection and Immunity Mar 2018, 86 (4) e00688-17; DOI: 10.1128/IAI.00688-17
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  • Article
    • ABSTRACT
    • INTRODUCTION
    • RESULTS
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KEYWORDS

Trypanosoma cruzi
Chagas disease
resolvins
resolvin D1
resolvin D5
resolvin E2
inflammation
immune modulation
eicosanoids
resolvin
host-parasite relationship

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