The Th17/Treg Ratio, IL-1RA and sCD14 Levels in Primary HIV Infection Predict the T-cell Activation Set Point in the Absence of Systemic Microbial Translocation

PLoS Pathogens

Laurence Meyer¹  Françoise Barré-Sinoussi²  Christine Rouzioux³  Pauline Campa³  Jean-Philippe Lavigne⁴  Céline Didier⁵  Laurence Weiss⁵  Catherine Dunyach-Rémy⁶  Maria Elena Manea⁶  Mathieu F. Chevalier⁶  Pierre-Marie Girard⁷  Daniel Scott-Algara⁸  Gaël Petitjean⁹ 

[1] AP-HP, Hôpital Européen Georges Pompidou, Paris, France;AP-HP, Hôpital Necker-Enfants Malades, Laboratoire de Virologie, Paris, France;AP-HP, Hôpital Saint-Antoine, Paris, France;INSERM U 1018, AP-HP, Université Paris Sud, Paris, France;INSERM U1047, Université Montpellier 1, UFR de Médecine, Nîmes, France;Institut Pasteur, Régulation des infections rétrovirales, Paris, France;Laboratoire de Bactériologie, CHU Carémeau, Nîmes, France;Université Paris Descartes, Sorbonne Paris Cité, Paris, France;Université Paris Diderot, Sorbonne Paris Cité, Paris, France

关键词: T cells;    Cytotoxic T cells;    HIV infections;    Monocytes;    Regulatory T cells;    Blood plasma;    Immune activation;    HIV;   

DOI  :  10.1371/journal.ppat.1003453

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Impairment of the intestinal barrier and subsequent microbial translocation (MT) may be involved in chronic immune activation, which plays a central role in HIV pathogenesis. Th17 cells are critical to prevent MT. The aim of the study was to investigate, in patients with primary HIV infection (PHI), the early relationship between the Th17/Treg ratio, monocyte activation and MT and their impact on the T-cell activation set point, which is known to predict disease progression. 27 patients with early PHI were included in a prospective longitudinal study and followed-up for 6 months. At baseline, the Th17/Treg ratio strongly negatively correlated with the proportion of activated CD8 T cells expressing CD38/HLA-DR or Ki-67. Also, the Th17/Treg ratio was negatively related to viral load and plasma levels of sCD14 and IL-1RA, two markers of monocyte activation. In untreated patients, the Th17/Treg ratio at baseline negatively correlated with CD8 T-cell activation at month 6 defining the T-cell activation set point (% HLA-DR+CD38+ and %Ki-67+). Soluble CD14 and IL-1RA plasma levels also predicted the T-cell activation set point. Levels of I-FABP, a marker of mucosal damages, were similar to healthy controls at baseline but increased at month 6. No decrease in anti-endotoxin core antibody (EndoCAb) and no peptidoglycan were detected during PHI. In addition, 16S rDNA was only detected at low levels in 2 out 27 patients at baseline and in one additional patient at M6. Altogether, data support the hypothesis that T-cell and monocyte activation in PHI are not primarily driven by systemic MT but rather by viral replication. Moreover, the “innate immune set point” defined by the early levels of sCD14 and IL-1RA might be powerful early surrogate markers for disease progression and should be considered for use in clinical practice.

【 授权许可】

CC BY