Analysis of the Trichuris suis excretory/secretory proteins as a function of life cycle stage and their immunomodulatory properties

• Published in: Scientific reports 2018-10, Vol.8 (1), p.15921-17, Article 15921
• Main Authors: Leroux, Louis-Philippe, Nasr, Mohamad, Valanparambil, Rajesh, Tam, Mifong, Rosa, Bruce A., Siciliani, Elizabeth, Hill, Dolores E., Zarlenga, Dante S., Jaramillo, Maritza, Weinstock, Joel V., Geary, Timothy G., Stevenson, Mary M., Urban, Joseph F., Mitreva, Makedonka, Jardim, Armando
• Format: Article
• Language: English
• Subjects: 13/21; 38; 38/23; 38/91; 631/250/2504/342; 631/250/255/1715; 631/337/2019; 631/337/475; 64/60; 82/58; 82/80; Animals; Arginase; Arginase - metabolism; Bone marrow; CD25 antigen; CD4 antigen; Cell proliferation; Cytokines - metabolism; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - metabolism; Foxp3 protein; Fractionation; Helminth Proteins - metabolism; Humanities and Social Sciences; Immunology; Immunomodulation; Immunomodulators; Immunoregulation; Inflammation; Interleukin 10; Interleukin 12; Kinases; Life Cycle Stages; Life cycles; Life Sciences; Lymphocytes T; Macrophages; Macrophages - cytology; Macrophages - metabolism; Mass spectrometry; Mass spectroscopy; multidisciplinary; Nitric oxide; Nitric Oxide - metabolism; Nucleoside-diphosphate kinase; Parasites; Proteins; Science; Science (multidisciplinary); Swine - parasitology; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - metabolism; Trichuris - growth & development; Trichuris - metabolism; Trichuris suis; Triose-phosphate isomerase; Tumor necrosis factor-α
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-34174-4

Parasitic worms have a remarkable ability to modulate host immune responses through several mechanisms including excreted/secreted proteins (ESP), yet the exact nature of these proteins and their targets often remains elusive. Here, we performed mass spectrometry analyses of ESP (TsESP) from larval and adult stages of the pig whipworm Trichuris suis (Ts) and identified ~350 proteins. Transcriptomic analyses revealed large subsets of differentially expressed genes in the various life cycle stages of the parasite. Exposure of bone marrow-derived macrophages and dendritic cells to TsESP markedly diminished secretion of the pro-inflammatory cytokines TNFα and IL-12p70. Conversely, TsESP exposure strongly induced release of the anti-inflammatory cytokine IL-10, and also induced high levels of nitric oxide (NO) and upregulated arginase activity in macrophages. Interestingly, TsESP failed to directly induce CD4 + CD25 + FoxP3 + regulatory T cells (T reg cells), while OVA-pulsed TsESP-treated dendritic cells suppressed antigen-specific OT-II CD4 + T cell proliferation. Fractionation of TsESP identified a subset of proteins that promoted anti-inflammatory functions, an activity that was recapitulated using recombinant T. suis triosephosphate isomerase (TPI) and nucleoside diphosphate kinase (NDK). Our study helps illuminate the intricate balance that is characteristic of parasite-host interactions at the immunological interface, and further establishes the principle that specific parasite-derived proteins can modulate immune cell functions.