Hemolytic Streptococcus may exacerbate kidney damage in IgA nephropathy through CCL20 response to the effect of Th17 cells

PLoS One. 2014 Sep 29;9(9):e108723. doi: 10.1371/journal.pone.0108723. eCollection 2014.

Abstract

Background: The exacerbation of IgA nephropathy (IgAN) is related to respiratory tract infection with hemolytic streptococcus (HS), but the mechanism is unknown. In this study we investigated the role of chemokine ligand 20 (CCL20) in response to the effect of T helper 17 (Th17) cells in the pathogenesis of IgAN associated with HS.

Methods: Thirty mice were randomly divided into five groups: control mice (control), IgAN mice (IgAN), HS-infected IgAN mice (HS-IgAN), CCL20-treated IgAN mice (CCL20-IgAN), and CCL20-treated HS infected IgAN mice (CCL20-HS-IgAN). IgAN mice were induced with lipopolysaccharide, carbon tetrachloride and bovine serum albumin. Then the mice were sensitized with CCL20 antibody and infected with alpha-hemolytic streptococcus (α-HS) isolated from tonsils in sequence. Urine Albumin-Creatinine ratio and sediments were measured. The pathological changes in kidney and lung tissues were observed under microscopy. Th17 cells and regulatory T cells (Tregs) in kidneys were tested by flow cytometry. CCL20, IL-17A, IL-6 and IL-21 in the kidneys were detected by ELISA.

Results: The IgAN mice had albuminuria and microscopic hematuria, renal mesangial proliferation, IgA deposition, high electron dense deposition in glomerular mesangial region, decreased frequency of Tregs, increased frequency of Th17 and Th17-Treg ratio. Furthermore, Th17-related cytokines CCL20, IL-17A, IL-6 and IL-21 were all increased in the kidneys of IgAN mice. Compared with IgAN mice, the manifestations in HS-IgAN mice were more severe, but alleviated in CCL20-treated groups.

Conclusion: α-HS may exacerbate kidney damage in IgAN through CCL20 response to the effect of Th17 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / metabolism
  • Animals
  • Antibodies / pharmacology
  • Chemokine CCL20 / metabolism*
  • Creatinine / metabolism
  • Disease Progression*
  • Female
  • Glomerulonephritis, IGA / immunology*
  • Glomerulonephritis, IGA / microbiology*
  • Glomerulonephritis, IGA / pathology
  • Hemolysis / drug effects
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / pathology*
  • Kidney Glomerulus / ultrastructure
  • Lung / drug effects
  • Lung / pathology
  • Mice, Inbred BALB C
  • Streptococcus / physiology*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • Th17 Cells / drug effects
  • Th17 Cells / immunology*

Substances

  • Albumins
  • Antibodies
  • Chemokine CCL20
  • Creatinine

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (nos. 81173401; 81270786) (http://www.nsfc.gov.cn/), and special grade of the financial support from China Postdoctoral Science Foundation (nos. 201003523) (http://res.chinapostdoctor.org.cn/Program/Main.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.