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Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

Jang, JC; Chen, G; Wang, SH; Barnes, MA; Chung, JI; Camberis, M; Le Gros, G; Cooper, PJ; Steel, C; Nutman, TB; et al. Jang, JC; Chen, G; Wang, SH; Barnes, MA; Chung, JI; Camberis, M; Le Gros, G; Cooper, PJ; Steel, C; Nutman, TB; Lazar, MA; Nair, MG (2015) Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden. PLoS Pathogens, 11 (1). ISSN 1553-7374 https://doi.org/10.1371/journal.ppat.1004579
SGUL Authors: Cooper, Philip John

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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.

Item Type: Article
Additional Information: This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Keywords: Virology, 0605 Microbiology, 1107 Immunology, 1108 Medical Microbiology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: PLoS Pathogens
Article Number: e1004579
ISSN: 1553-7374
Language: eng
Dates:
DateEvent
8 January 2015Published
Projects:
Project IDFunderFunder ID
R01 AI091759NIAID NIH HHSUNSPECIFIED
PubMed ID: 25568944
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107354
Publisher's version: https://doi.org/10.1371/journal.ppat.1004579

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