RNA helicase activity in the immune system: a matter of sex chromosomes

11/02/2019

The proverbial differences between sexes are also found in many biological processes. Immune responses for example have for a long time been known to have distinct differences between males and females. Scientists from Thomas Decker’s group in collaboration with other research institutes now add another piece in the puzzle of sex related differences in immunity.

When human organisms are infected by pathogens, a cascade of molecular signals makes sure the immune system correctly reacts to the invaders. On a genetic level so called RNA helicases play an important role. These enzymes are capable of “unpacking” the genome by separating the strands of the DNA double helix but also catalyse metabolic processes of RNA including the synthesis of transcripts of antimicrobial genes. The scientists created organisms lacking the RNA helicase DDX3X. Their results show that DDX3X supports decoding of genes, thus making important contributions to the activation of macrophages, essential white blood cells that engulf and destroy pathogens. Also, production of certain white blood cells is impaired causing an inability to combat infection with bacteria. Thus, DDX3X plays an essential role in the antibacterial immune response.

The DDX3X gene has a counterpart on the male Y chromosome called DDX3Y. This means that male organisms lacking DDX3X still have a copy of DDX3Y. Male organisms survived a lack of DDX3X better than their female counterparts, indicating that that the presence of the Y Chromosome is able to compensate for the loss of DDX3X. The role of the male RNA helicase and its function in other bacteria remains elusive, yet the two enzymes share a high degree of similarity, hinting that DDX3Y could be a key factor in differences in innate immunity in humans.

“It has been known for many years that antibacterial immune responses differ between sexes. Known causes for this difference include immunological activities of sex hormones or different microbiota. With DDX3X we were able to identify a monogenic cause of immunological differences between sexes. Future studies must reveal in how far our results translate to humans and whether they are of relevance for gender-tailored manipulation of the immune system during diseases”, group leader Thomas Decker concludes.

Publication in PLOS Pathogens: 

Szappanos D, Tschismarov R, Perlot T, Westermayer S, Fischer K, Platanitis E, Kallinger F1, Novatchkova M, Lassnig C, Müller M, Sexl V, Bennett KL, Foong-Sobis M, Penninger JM, Decker T.

The RNA helicase DDX3X is an essential mediator of innate antimicrobial immunity.

DOI: 10.1371/journal.ppat.1007397