Pivotal role of M-DC8+ monocytes from viremic HIV-infected patients in TNF overproduction in response to microbial products

Inserm U1016, Institut Cochin, Paris, France
Blood (Impact Factor: 9.78). 07/2012; 120(11):2259-68. DOI: 10.1182/blood-2012-03-418681
Source: PubMed

ABSTRACT HIV infects activated CD4(+) T cells and induces their depletion. Progressive HIV infection leading to AIDS is fueled by chronic immune hyperactivation, mediated by inflammatory cytokines like TNFα. This has been related to intestinal epithelial damage and microbial LPS translocation into the circulation. Using 11-color flow cytometry, cell sorting, and cell culture, we investigated the numbers and TNFα production of fully defined circulating dendritic cell and monocyte populations during HIV-1 infection. In 15 viremic, untreated patients, compared with 8 treated, virologically suppressed patients or to 13 healthy blood donors, circulating CD141 (BDCA-3)(+) and CD1c (BDCA-1)(+) dendritic cell counts were reduced. Conversely, CD14(+)CD16(++) monocyte counts were increased, particularly those expressing M-DC8, while classical CD14(++)CD16(-)M-DC8(-) monocyte numbers were unchanged. Blood mononuclear cells from viremic patients produced more TNFα in response to LPS than those from virologically suppressed patients. M-DC8(+) monocytes were mostly responsible for this overproduction. Moreover, M-DC8(+) monocytes differentiated in vitro from classical monocytes using M-CSF and GM-CSF, which is increased in viremic patient's plasma. This M-DC8(+) monocyte population, which is involved in the pathogenesis of chronic inflammatory diseases like Crohn disease, might thus be considered as a major actor in the immune hyperactivation fueling HIV infection progression.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Seafood is a very potent allergen. Epidemiological studies of seafood allergy in the highly exposed cooking profession are lacking. The objective of this first case series was to demonstrate the high relevance and consequences of seafood allergy in cooks.Patients und Methods Retrospective analysis of all the case files sent in which the presence of an occupational disease according to no. 5101 of the appendix of the German ordinance on industrial disease was to be clarified.ResultsThirty cooks (men 70 %) with an occupational seafood allergy were assessed between January 2008 and April 2014. Seafood allergy was observed in young workers (median age 24.7 yrs.) with an early manifestation of the disease (after median employment time of 1.7 years). In all except one (96.7 %) onset was localized on the hands. Most commonly documented were immediate sensitizations to cod, salmon, trout, and herring. Emergency treatment due to an anaphylactic shock at the workplace became necessary in 5 cases (16.7 %). In 27 cases (90 %) discontinuation of occupation was needed and occurred after a median job period of 6.3 years.Conclusions Seafood allergy in cooks is mostly characterized by a quick progressive course of disease, generally at the start of the cooking career. The prognosis for continuance in occupation is poor and an occupational disease must be considered at an early stage. An emergency kit with an epinephrine auto-injector should be provided for life by the responsible accident insurer.
    Journal der Deutschen Dermatologischen Gesellschaft 10/2014; 12(10). DOI:10.1111/ddg.12456 · 1.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bacterial sepsis is an important cause of morbidity and mortality in patients with HIV. HIV causes increased susceptibility to invasive infections and affects sepsis pathogenesis caused by pre-existing activation and exhaustion of the immune system. We review the effect of HIV on different components of immune responses implicated in bacterial sepsis, and possible mechanisms underlying the increased risk of invasive bacterial infections. We focus on pattern recognition receptors and innate cellular responses, cytokines, lymphocytes, coagulation, and the complement system. A combination of factors causes increased susceptibility to infection and can contribute to a disturbed immune response during a septic event in patients with HIV. HIV-induced perturbations of the immune system depend on stage of infection and are only in part restored by combination antiretroviral therapy. Immunomodulatory treatments currently under development for sepsis might be particularly beneficial to patients with HIV co-infection because many pathogenic mechanisms in HIV and sepsis overlap. Copyright © 2014 Elsevier Ltd. All rights reserved.
    The Lancet Infectious Diseases 10/2014; 15(1). DOI:10.1016/S1473-3099(14)70917-X · 19.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Owing to ongoing recognition of pathogen-associated molecular patterns, immune activation and upregulation of IFN-stimulated genes (ISGs) are sustained in the chronically infected host. Albeit most ISGs are important effectors for containing viral replication, some might exert compensatory immune suppression to limit pathological dysfunctions, although the mechanisms are not fully understood. In this study, we report that the ISG lymphocyte Ag 6 complex, locus E (LY6E) is a negative immune regulator of monocytes. LY6E in monocytes negatively modulated CD14 expression and subsequently dampened the responsiveness to LPS stimulation in vitro. In the setting of chronic HIV infection, the upregulation of LY6E was correlated with reduced CD14 level on monocytes; however, the immunosuppressive effect of LY6E was not adequate to remedy the hyperresponsiveness of activated monocytes. Taken together, the regulatory LY6E pathway in monocytes represents one of negative feedback mechanisms that counterbalance monocyte activation, which might be caused by LPS translocation through the compromised gastrointestinal tract during persistent HIV-1 infection and may serve as a potential target for immune intervention.
    The Journal of Immunology 09/2014; 193(8). DOI:10.4049/jimmunol.1401249 · 5.36 Impact Factor


Available from
May 21, 2014

Similar Publications