Acute kidney injury in a mouse model of meningococcal disease

Int J Immunopathol Pharmacol. 2021 Jan-Dec:35:20587384211056507. doi: 10.1177/20587384211056507.

Abstract

Introduction: Meningococcal disease is associated with high mortality. When acute kidney injury (AKI) occurs in patients with severe meningococcal disease, it is typically attributable to sepsis, although meningococcal disease and lipopolysaccharide release are rarely investigated. Therefore, we evaluated renal tissue in a mouse model of meningococcal disease.

Methods: Female BALB/c mice were induced to AKI by meningococcal challenge. Markers of renal function were evaluated in infected and control mice.

Results: In the infected mice, serum concentrations of tumor necrosis factor alpha, interferon gamma, interleukins (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, and IL-12), and granulocyte-macrophage colony-stimulating factor were elevated, as was renal interstitial infiltration with lymphocytes and neutrophils (p < 0.01 for the latter). Histological analysis showed meningococcal microcolonies in the renal interstitium, without acute tubular necrosis. Infected mice also showed elevated renal expression of toll-like receptor 2, toll-like receptor 4, and Tamm-Horsfall protein. The expression of factors in the intrinsic pathway of apoptosis was equal to or lower than that observed in the control mice. Urinary sodium and potassium were also lower in infected mice, probably due to a tubular defect.

Conclusion: Our findings corroborate those of other studies of AKI in sepsis. To our knowledge, this is the first time that meningococci have been identified in renal interstitium and that the resulting apoptosis and inflammation have been evaluated. However, additional studies are needed in order to elucidate the mechanisms involved.

Keywords: acute kidney injury; citokines; immunology; meningococcal disease.

MeSH terms

  • Acute Kidney Injury* / blood
  • Acute Kidney Injury* / etiology
  • Acute Kidney Injury* / immunology
  • Acute Kidney Injury* / pathology
  • Animals
  • Disease Models, Animal
  • Gene Expression Profiling / methods
  • Granulocyte-Macrophage Colony-Stimulating Factor / analysis
  • Interleukins / analysis
  • Kidney* / immunology
  • Kidney* / microbiology
  • Kidney* / pathology
  • Meningococcal Infections* / complications
  • Meningococcal Infections* / immunology
  • Mice
  • Mice, Inbred C57BL
  • Necrosis
  • Neisseria meningitidis / isolation & purification*
  • Neutrophil Infiltration
  • Toll-Like Receptor 2 / analysis
  • Toll-Like Receptor 4 / analysis
  • Uromodulin / analysis

Substances

  • Interleukins
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Umod protein, mouse
  • Uromodulin
  • Granulocyte-Macrophage Colony-Stimulating Factor