MyD88-NF-kB Signalling Pathway Contributes to Plasmodium Falciparum Infected Malaria Severity: A Tribal Patient Based Study from Assam

Background: Severe Plasmodium falciparum malaria is characterized by dysregulated host inflammatory responses that contribute significantly to disease pathogenesis. The MyD88–NF-κB signaling pathway plays a central role in Toll-like receptor-mediated innate immune activation, yet its contribution to malaria severity among ethnically distinct tribal populations of Northeast India remains inadequately explored.

Methods: This case-control study enrolled 64 P. falciparum-infected tribal patients (53 uncomplicated malaria and 11 severe malaria) and 88 age-, sex-, and community-matched healthy controls from Assam, India. The mRNA expression of MyD88, NF-κB p65, and TNF-α was quantified by real-time PCR, while serum NF-κB protein levels were determined by ELISA. Monocyte (CD14⁺) expression was analyzed by flow cytometry, and associations with disease severity were evaluated statistically.

Results: Malaria patients exhibited significantly elevated MyD88, NF-κB p65, and TNF-α expression compared with healthy controls, with the highest levels observed in severe malaria cases. MyD88 expression correlated positively with NF-κB p65 (Spearman's ρ = 0.673, p = 0.048) and TNF-α expression (ρ = 0.714, p = 0.006) in severe malaria, indicating activation of the MyD88-dependent inflammatory cascade. CD14⁺ monocyte expression was also significantly increased in malaria patients, particularly in severe disease.

Conclusions: Enhanced activation of the MyD88–NF-κB signaling axis is strongly associated with inflammatory amplification and disease severity in P. falciparum malaria. These findings highlight the pathway as a potential prognostic biomarker and therapeutic target for severe malaria in endemic tribal populations.