Differential Expression Levels of Inflammatory Chemokines and TLRs in Patients Suffering from Mild and Severe Japanese Encephalitis.

Abstract

Japanese encephalitis (JE) is a vector-borne viral disease with clinical manifestations ranging from asymptomatic to severe neurological symptoms and even leading to death. The exact pathophysiology for diverse clinical spectrum of the disease is complex and has not yet been defined. Studies have postulated that during JE infection, inflammatory cytokines and chemokines are produced after the initial recognition of viral antigens through the engagement of toll-like receptors (TLR) pathways. However, there is paucity of knowledge on the expression levels of chemokines and TLRs among mild and severely affected JE patients. Hence, to better understand disease pathogenesis, we examined the mRNA expression of chemokines, CCL2 and CCL5, and their respective receptors CCR2 and CCR5 along with TLRs viz. TLR3, TLR7, TLR8, and TLR9 in context of mild and severely Japanese encephalitis virus (JEV)-infected (n = 19) and healthy (n = 19) individuals. Our study showed significant downregulation of CCL2, CCL5, CCR2, CCR5, and TLR3 by log 0.87, 1.02, 0.82, 0.68, and 0.37-fold respectively, among mild cases compared with controls. Significant difference of gene expression among mild and severe JE cases for CCL2 (p < 0.001), CCL5 (p < 0.01), and TLR7 (p < 0.05) was observed. In conclusion, our results proposes that chemokines viz. CCL2 and CCL5 along with TLR7 may be associated with degree of pathogenesis of JE and could be putative therapeutic targets for preventing severe inflammation during viral encephalitis.