Impact of Strongyloides stercoralis infection on complement activation in Type 2 diabetes mellitus: Insights from a clinical and anthelmintic intervention study

PLoS Negl Trop Dis. 2024 Apr 2;18(4):e0012048. doi: 10.1371/journal.pntd.0012048. eCollection 2024 Apr.

Abstract

Background: Numerous studies indicate a potential protective role of helminths in diabetes mellitus (DM) progression. The complement system, vital for host defense, plays a crucial role in tissue homeostasis and immune surveillance. Dysregulated complement activation is implicated in diabetic complications. We aimed to investigate the influence of the helminth, Strongyloides stercoralis (Ss) on complement activation in individuals with type 2 DM (T2D).

Methodology: We assessed circulating levels of complement proteins (C1q, C2, C3, C4, C4b, C5, C5a, and MBL (Lectin)) and their regulatory components (Factor B, Factor D, Factor H, and Factor I) in individuals with T2D with (n = 60) or without concomitant Ss infection (n = 58). Additionally, we evaluated the impact of anthelmintic therapy on these parameters after 6 months in Ss-infected individuals (n = 60).

Results: Ss+DM+ individuals demonstrated reduced levels of complement proteins (C1q, C4b, MBL (Lectin), C3, C5a, and C3b/iC3b) and complement regulatory proteins (Factor B and Factor D) compared to Ss-DM+ individuals. Following anthelmintic therapy, there was a partial reversal of these levels in Ss+DM+ individuals.

Conclusion: Our findings indicate that Ss infection reduces complement activation, potentially mitigating inflammatory processes in individuals with T2D. The study underscores the complex interplay between helminth infections, complement regulation, and diabetes mellitus, offering insights into potential therapeutic avenues.

MeSH terms

  • Animals
  • Anthelmintics* / therapeutic use
  • Complement Activation
  • Complement C1q
  • Complement Factor B
  • Complement Factor D / therapeutic use
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Helminths*
  • Humans
  • Lectins
  • Strongyloides stercoralis*
  • Strongyloidiasis* / complications
  • Strongyloidiasis* / drug therapy

Substances

  • Complement Factor B
  • Complement Factor D
  • Complement C1q
  • Anthelmintics
  • Lectins

Grants and funding

This work was supported by the Division of Intramural Research, the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institutes of Health (NIH) (AI-001065-08) to SB.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.