Peripheral natural killer cells in chronic hepatitis B patients display multiple molecular features of T cell exhaustion

eLife

Sophie Alain¹  Marine Pujol¹  Annabelle Drouillard¹  David Durantel²  Thierry Walzer²  Marine Villard³  Michelle Ainouze³  Yamila Rocca³  Marie Marotel³  Melissa Gomez³  Laurie Besson³  Issam Tout³  Guillaume Roblot³  Omran Allatif³  Veronique Loustaud³  Sébastien Viel³  Antoine Marçais⁴  Uzma Hasan⁵ 

[1] Service d’Immunologie biologique, Hôpital Lyon Sud, Hospices Civils de Lyon, Lyon, France;CHU Limoges, Service d’Hépatogastroentérologie, U1248 INSERM, Université Limoges, Limoges, France;CIRI, Centre International de Recherche en Infectiologie, Team Innate Immunity in Infectious and Autoimmune Diseases, Univ Lyon, Inserm, Université Claude Bernard Lyon 1, CNRS, Lyon, France;Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM, U1052, CNRS, Université de Lyon, Lyon, France;Département de Microbiologie, CHU de Limoges, Faculté de médecine-Université de Limoges, Limoges, France;

关键词: natural killer;    dysfunction;    calcium pathway;    mTOR;   

DOI  :  10.7554/eLife.60095

来源: DOAJ

【 摘 要 】

Antiviral effectors such as natural killer (NK) cells have impaired functions in chronic hepatitis B (CHB) patients. The molecular mechanism responsible for this dysfunction remains poorly characterised. We show that decreased cytokine production capacity of peripheral NK cells from CHB patients was associated with reduced expression of NKp30 and CD16, and defective mTOR pathway activity. Transcriptome analysis of patients NK cells revealed an enrichment for transcripts expressed in exhausted T cells suggesting that NK cell dysfunction and T cell exhaustion employ common mechanisms. In particular, the transcription factor TOX and several of its targets were over-expressed in NK cells of CHB patients. This signature was predicted to be dependent on the calcium-associated transcription factor NFAT. Stimulation of the calcium-dependent pathway recapitulated features of NK cells from CHB patients. Thus, deregulated calcium signalling could be a central event in both T cell exhaustion and NK cell dysfunction occurring during chronic infections.

【 授权许可】

Unknown