Increased accumulation of regulatory granulocytic myeloid cells in mannose receptor C type 1-deficient mice correlates with protection in a mouse model of neurocysticercosis

Infect Immun. 2013 Apr;81(4):1052-63. doi: 10.1128/IAI.01176-12. Epub 2013 Jan 14.

Abstract

Neurocysticercosis (NCC) is a central nervous system (CNS) infection caused by the metacestode stage of the parasite Taenia solium. During NCC, the parasites release immunodominant glycan antigens in the CNS environment, invoking immune responses. The majority of the associated pathogenesis is attributed to the immune response against the parasites. Glycans from a number of pathogens, including helminths, act as pathogen-associated molecular pattern molecules (PAMPs), which are recognized by pattern recognition receptors (PRRs) known as C-type lectin receptors (CLRs). Using a mouse model of NCC by infection with the related parasite Mesocestoides corti, we have investigated the role of mannose receptor C type 1 (MRC1), a CLR which recognizes high-mannose-containing glycan antigens. Here we show that MRC1(-/-) mice exhibit increased survival times after infection compared with their wild-type (WT) counterparts. The decreased disease severity correlates with reduced levels of expression of markers implicated in NCC pathology, such as interleukin-1β (IL-1β), IL-6, CCL5, and matrix metalloproteinase 9 (MMP9), in addition to induction of an important repair marker, fibroblast growth factor 2 (FGF2). Furthermore, the immune cell subsets that infiltrate the brain of MRC1(-/-) mice are dramatically altered and characterized by reduced numbers of T cells and the accumulation of granulocytic cells with an immune phenotype resembling granulocytic myeloid-dependent suppressor cells (gMDSCs). The results suggest that MRC1 plays a critical role in myeloid plasticity, which in turn affects the adaptive immune response and immunopathogenesis during murine NCC.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / immunology
  • Brain / pathology
  • Cytokines / metabolism
  • Female
  • Granulocyte Precursor Cells / immunology*
  • Lectins, C-Type / deficiency*
  • Lectins, C-Type / metabolism
  • Mannose Receptor
  • Mannose-Binding Lectins / deficiency*
  • Mannose-Binding Lectins / metabolism
  • Membrane Glycoproteins / deficiency*
  • Membrane Glycoproteins / metabolism
  • Mesocestoides / immunology*
  • Mesocestoides / pathogenicity
  • Mice
  • Mice, Inbred C57BL
  • Neurocysticercosis / immunology*
  • Neurocysticercosis / mortality
  • Neurocysticercosis / pathology
  • Receptors, Cell Surface / deficiency*
  • Receptors, Cell Surface / metabolism
  • Receptors, Immunologic
  • Severity of Illness Index
  • Survival Analysis

Substances

  • Cytokines
  • Lectins, C-Type
  • MRC1 protein, mouse
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, Immunologic