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Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and
Jessica C Jang1, Gang Chen1, Spencer H Wang1
1Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California, United States of America.
Abstract:
Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology.
Insights
Human resistin exacerbates helminth infections by promoting inflammation and delaying parasite clearance. Targeting resistin could offer new strategies for treating helminth infections and related immune pathologies.
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- Parasitic helminth infections cause significant morbidity, including immune-mediated organ failure.
- Understanding host immune responses to helminths is crucial for developing new treatments.
- The role of human resistin (hResistin) in helminth infection was previously unknown.
Purpose of the Study:
- To investigate the function of human resistin in helminth infection.
- To determine if hResistin influences the host immune response and parasite clearance.
Main Methods:
- Utilized transgenic mice expressing the human resistin gene (hRetnTg+).
- Infected mice with Nippostrongylus brasiliensis (Nb) and analyzed host responses.
- Performed genome-wide transcriptional profiling of infected lung tissue.
- Examined serum resistin levels in human helminth infections.
Main Results:
- hResistin expression was upregulated in infected tissues of hRetnTg+ mice.
- hRetnTg+ mice showed exacerbated inflammation, increased monocyte infiltration, and delayed parasite expulsion.
- hResistin promoted proinflammatory cytokines and toll-like receptor signaling.
- Increased serum resistin correlated with parasite load and proinflammatory cytokines in humans.
Conclusions:
- Human resistin acts as a detrimental factor in helminth infections.
- hResistin promotes inflammation and hinders parasite clearance.
- Targeting the resistin/cytokine axis may offer novel therapeutic and diagnostic approaches for helminth infections.

