Systemic effects in naïve mice injected with immunomodulatory lectin ArtinM

PLoS One. 2017 Oct 30;12(10):e0187151. doi: 10.1371/journal.pone.0187151. eCollection 2017.

Abstract

Toll-like receptors (TLR) contain N-glycans, which are important glycotargets for plant lectins, to induce immunomodulation. The lectin ArtinM obtained from Artocarpus heterophyllus interacts with TLR2 N-glycans to stimulate IL-12 production by antigen-presenting cells and to drive the immune response toward the Th1 axis, conferring resistance against intracellular pathogens. This immunomodulatory effect was demonstrated by subcutaneously injecting (s.c.) ArtinM (0.5 μg) in infected mice. In this study, we evaluated the systemic implications of ArtinM administration in naïve BALB/c mice. The mice were s.c. injected twice (7 days interval) with ArtinM (0.5, 1.0, 2.5, or 5.0 μg), LPS (positive control), or PBS (negative control) and euthanized after three days. None of the ArtinM-injected mice exhibited change in body weight, whereas the relative mass of the heart and lungs diminished in mice injected with the highest ArtinM dose (5.0 μg). Few and discrete inflammatory foci were detected in the heart, lung, and liver of mice receiving ArtinM at doses ≥2.5 μg. Moreover, the highest dose of ArtinM was associated with increased serum levels of creatine kinase MB isoenzyme (CK-MB) and globulins as well as an augmented presence of neutrophils in the heart and lung. IL-12, IFN-γ, TNF-α, and IL-10 measurements in the liver, kidney, spleen, heart, and lung homogenates revealed decreased IL-10 level in the heart and lung of mice injected with 5.0 μg ArtinM. We also found an augmented frequency of T helper and B cells in the spleen of all ArtinM-injected naïve mice, whereas the relative expressions of T-bet, GATA-3, and ROR-γt were similar to those in PBS-injected animals. Our study demonstrates that s.c. injection of high doses of ArtinM in naïve mice promotes mild inflammatory lesions and that a low immunomodulatory dose is innocuous to naïve mice.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Body Weight / drug effects
  • Chromatography, Affinity
  • Cytokines / metabolism
  • Lectins / administration & dosage*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Organ Size / drug effects

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • Lectins

Grants and funding

This research was financially supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (grant numbers 2012/09611-0, 2013/04088-0, 2014/16003-1, 2016/04877-2, 2016/10446-4, 2016/23112-7), Fundação de Amparo a Pesquisa do Estado de Minas Gerais/Universidade Federal do Triângulo Mineiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico (475357/2013-2), Financiadora de Estudos e Projetos (0110045900), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior and Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto.