Ferritin heavy chain‐mediated iron homoeostasis regulates expression of IL‐10 in Chlamydia trachomatis ‐infected HeLa cells

Abstract

Chlamydia trachomatis is the leading cause of sexually transmitted infection worldwide, in which disease outcome is determined by the balance between pro‐ and anti‐inflammatory host immune responses. Iron plays important roles in regulation and enhancement of various pro‐ and anti‐inflammatory cytokines. Earlier studies have established essentiality of iron in C. trachomatis infection; however, there is lack of study wherein modulatory effect of iron regulated protein [FHC (ferritin heavy chain)] in regulation of anti‐inflammatory cytokine IL (interleukin)‐10 has been investigated. In this study, immunoblotting results showed the up‐regulation of FHC in C. trachomatis ‐infected HeLa cells in comparison with mock ( in vitro control). Further secretory IL‐10 level was significantly increased ( P <0.001) or decreased ( P <0.001) in response to iron supplementation [FAC (ferric ammonium citrate)] and depletion [DFO (deferoxamine)], respectively. However, in C. trachomatis ‐infected HeLa cells, levels of IL‐10 remain higher, irrespective of availability of iron in comparison with their respective control. These results showed that secretion of IL‐10 and expressions of FHC have concordance. Further, to understand interdependence of IL‐10 and iron homoeostasis (regulation), the levels of IL‐10 were compared with iron‐responsive GFP (green fluorescent protein) expression in HeLa‐229 cells. The mean fluorescent intensities of GFP were in accordance with levels of IL‐10 in C. trachomatis ‐infected cells. These results showed the association of secreted IL‐10, FHC and iron homoeostasis in C. trachomatis ‐infected HeLa‐229 cells. This study provides insight into host– Chlamydia interaction at the crossroad of iron metabolism and immune responses and may help in realizing the potential of iron homoeostasis modulators in treatment of chronic chlamydial infection.