Neutrophils in antiretroviral therapy-controlled HIV demonstrate hyperactivation associated with a specific IL-17/IL-22 environment

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:134

Article

Campillo-Gimenez, Laure^1,2  Casulli, Sarah^1,2  Dudoit, Yasmine^3,4  Seang, Sophie^3,4  Carcelain, Guislaine^2,5  Lambert-Niclot, Sidonie^4,6  Appay, Victor²  Autran, Brigitte^2,5  Tubiana, Roland^3,4  Elbim, Carole^1,2 

[1] UPMC Univ Paris 06, Sorbonne Univ, Paris, France

[2] INSERM, Ctr Immunol & Malad Infect, UMR S CR7, U1135, F-75013 Paris, France

[3] Hop La Pitie Salpetriere, AP HP, Serv Malad Infect & Trop, Paris, France

[4] UPMC Univ Paris 06, Sorbonne Univ, Pierre Louis Inst Epidemiol & Publ Hlth, UMR S 1136, Paris, France

[5] Hop La Pitie Salpetriere, AP HP, Lab Immunol Cellulaire & Tissulaire, Paris, France

[6] Hop La Pitie Salpetriere, AP HP, Lab Virol, Paris, France

关键词: Neutrophils;    HIV;    inflammation;    IL-18;    IL-17;    IL-22;   

DOI  :  10.1016/j.jaci.2014.05.040

来源: Elsevier

【 摘 要 】

Background: Despite control of HIV infection under antiretroviral therapy (ART), immune T-cell activation persists in patients with controlled HIV infection, who are at higher risk of inflammatory diseases than the general population. PMNs play a key role in host defenses against invading microorganisms but also potentiate inflammatory reactions in cases of excessive or misdirected responses. Objective: The aim of our study was to analyze PMN functions in 60 ART-treated and controlled HIV-infected patients (viral load, <20 RNA copies/mL; CD4 count, >= 350 cells/mm(3)) with (HIV[I] group) and without (HIV[NI] group) diseases related to an inflammatory process and to compare them with 22 healthy control subjects. Methods: Flow cytometry was used to evaluate PMN functions in whole-blood conditions. We studied in parallel the activation markers of T lymphocytes and monocytes and the proinflammatory cytokine environment. Results: Blood samples from HIV-infected patients revealed basal PMN hyperactivation associated with deregulation of the apoptosis/necrosis equilibrium. Interestingly, this hyperactivation was greater in HIV(I) than HIV(NI) patients and contrasted with a lack of monocyte activation in both groups. The percentage of circulating cells producing IL-17 was also significantly higher in HIV-infected patients than in control subjects and was positively correlated with markers of basal PMN activation. In addition, the detection of IL-22 overproduction in HIV(NI) patients suggests that it might contribute to counteracting chronic inflammatory processes during HIV infection. Conclusions: This study thus demonstrates the presence of highly activated PMNs in HIV-infected patients receiving effective ART and the association of these cells with a specific IL-17/IL-22 environment.

【 授权许可】

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