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Tropheryma whipplei Increases Expression of Human Leukocyte Antigen-G on Monocytes to Reduce Tumor Necrosis Factor and Promote Bacterial Replication.

Abstract：

BACKGROUND & AIMS:Infection with Tropheryma whipplei has a range of effects-some patients can be chronic carriers without developing any symptoms, whereas others can develop systemic Whipple disease, characterized by a lack a protective inflammatory immune response. Alterations in HLA-G function have been associated with several diseases. We investigated the role of HLA-G during T whipplei infection. METHODS:Sera, total RNA, and genomic DNA were collected from peripheral blood from 22 patients with classic Whipple's disease, 19 patients with localized T whipplei infections, and 21 asymptomatic carriers. Levels of soluble HLA-G in sera were measured by enzyme-linked immuosorbent assay, and expressions of HLA-G and its isoforms were monitored by real-time polymerase chain reaction. HLA-G alleles were identified and compared with a population of voluntary bone marrow donors. Additionally, monocytes from healthy subjects were stimulated with T whipplei, and HLA-G expression was monitored by real-time polymerase chain reaction and flow cytometry. Bacterial replication was assessed by polymerase chain reaction in the presence of HLA-G or inhibitor of tumor necrosis factor (TNF) (etanercept). RESULTS:HLA-G mRNAs and levels of soluble HLA-G were significantly increased in sera from patients with chronic T whipplei infection compared with sera from asymptomatic carriers and control individuals. No specific HLA-G haplotypes were associated with disease or T whipplei infection. However, T whipplei infection of monocytes induced expression of HLA-G, which was associated with reduced secretion of TNF compared with noninfected monocytes. A neutralizing antibody against HLA-G increased TNF secretion by monocytes in response to T whipplei, and a TNF inhibitor promoted bacteria replication. CONCLUSIONS:Levels of HLA-G are increased in sera from patients with T whipplei tissue infections, associated with reduced production of TNF by monocytes. This might promote bacteria colonization in patients.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Ben Azzouz E,Boumaza A,Mezouar S,Bardou M,Carlini F,Picard C,Raoult D,Mège JL,Desnues B

doi

10.1053/j.gastro.2018.07.034

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

1553-1563

issue

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(18)34822-4

journal_volume

155

pub_type

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Tropheryma whipplei Increases Expression of Human Leukocyte Antigen-G on Monocytes to Reduce Tumor Necrosis Factor and Promote Bacterial Replication.