Helminth infections, including hookworms and Schistosomes, can cause severe disability and death. Infection management and control would benefit from identification of biomarkers for early detection and prognosis. While animal models suggest that Trefoil Factor Family proteins (TFF2 and TFF3) and interleukin-33 (IL-33)-driven type 2 immune responses are critical mediators of tissue repair and worm clearance in the context of hookworm infection, very little is known about how they are modulated in the context of human helminth infection. We measured TFF2, TFF3, and IL-33 levels in serum from patients in Brazil infected with Hookworm and/or Schistosomes, and compared them to endemic and non-endemic controls. TFF2 was specifically elevated by Hookworm infection, not Schistosoma or co-infection. This elevation was more strongly correlated with age than with worm burden. To determine if this might apply more broadly to other species or regions, we measured TFFs and cytokine levels in both the serum and urine of Nigerian school children infected with S. haematobium. We found that serum levels of TFF2 and 3 were reduced by infection, but urine cytokine levels were increased (IL-1β, TNFα, IL-13, and IL-10). Finally, to determine if TFF2 and 3 might have immunosuppressive effects, we treated stimulated or unstimulated PMBCs with recombinant human TFF2 or TFF3 and measured proinflammatory cytokine levels. We found that rhTFF2, but not rhTFF3, was able to suppress TNF alpha and IFN gamma release from stimulated human PMBCs. Taken together, these data support a role for TFF proteins in human helminth infection.
Tests for Serum Levels of Trefoil Factor Family Proteins Can Improve Gastric Cancer Screening