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

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. Author summary: Our research delves into the intricate link between Strongyloides stercoralis, a microscopic worm, and diabetes. Within our body, we possess a defense mechanism known as the complement system, essential for overall well-being. However, diabetes can disrupt this system. Our study aimed to uncover whether the presence of Ss infection influence this process. Individuals with both diabetes and Ss infection displayed lower levels of specific proteins associated with the complement system. Intriguingly, treating the Ss infection led to a partial restoration of these protein levels. This suggests that the Ss infection might play a role in curbing inflammation associated with diabetes. The unexpected alliance between this Ss infection and our body opens new avenues for potential therapies. This study highlights the complexity of interactions within our immune system and offers insights into how unanticipated allies might contribute to managing diabetes. Understanding such connections could pave the way for innovative approaches to diabetes treatment, emphasizing the importance of exploring unconventional aspects of our biological defenses.